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Meeting Materials (Special User login required)
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Allison Martin, M.D. (Ex Officio)
Elin Sigurdson, M.D.
Nagalingam Suntharalingam, Ph.D.
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Mitchell Machtay, M.D
Ramses Sadek, Ph.D.
Meihua Wang, Ph.D.
Kathryn Winter, M.S
Thomas J. Wudarski, M.S.
Via Telephone:
Kenneth Rosenzweig, M.D.
Ann O'Mara, Ph.D., R.N. (Ex Officio)
Susan Chung, M.D.
Absent:
Kate Murphy
Norman Wolmark, M.D.
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Interim Analysis
Brain
The first protocol-specified interim analyses for possible early reporting of efficacy results for
RTOG 9813, A Phase III Randomized Study of Radiation Therapy and Temozolomide (IND #60,265) versus Radiation Therapy and Nitrosourea for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (astrocytoma dominant), which was designed to test whether the addition of chemotherapy (temozolemide) to radiation therapy (RT) prolonged overall survival was presented by Meihua Wang, Ph.D., the study statistician.
Dr Wang presented a summary of the accrual for the study. RTOG 9813 was activated June 16, 2000. The study sample size was 454. There were two pilot arms in the Phase I component of the study, fifteen patients were enrolled on Pilot #1, which closed on March 15, 2001 and fourteen patients were enrolled on Pilot #2, which was closed on January 25, 2002. It was determined that the combination of RT + temozolomide + BCNU is not feasible.
The Phase III component was opened on October 15, 2002 and closed March 30, 2007 due to not meeting target accrual.
Dr. Wang also presented a review of the radiotherapy and chemotherapy toxicities.
The recommendation of the study statistician not to report at this time since the p-value is not less than the nominal significant level of 0.005 and the conditional power of 0.21 is bigger than 0.15; therefore the current data do not indicate a statistically significant difference in overall survival between the two arms. The second interim analysis will occur after 104 deaths have been observed.
The DMC concurred with the Group's recommendation.
RTOG Open Accruing Phase III Trials: Accrual and Toxicity Reviews
Brain
0320 - WBRT +SRS vs. WBRT + SRS + Temozolomide and WBRT + SRS + Erlotnib in Patients with NSCLC and 1-3 Brain Metastases
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
0525 - Conventional Adjuvant Temozolomide vs. Dose-Intensive Temozolomide in Patients with Newly Diagnosed Glioblastoma
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
H&N
0522 - CRT+/- C225for Advanced H&N Cancer
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
GU
0126 - High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
0232 - A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
An amendment to change the endpoint has been submitted.
0415 - Hypofractionated 3D-CRT/IMRT vs. Conventionally Fractionated 3D-CRT/IMRT in Patients with Favorable-Risk Prostate Cancer
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
0521 - A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs. AS and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Predeisone for Localized, High-Risk Prostate Cancer
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
Symptom Management
0435 - A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin for the Reduction of Oral Mucositis in Patients with Locally Advanced Head and Neck Cancer Receiving Radiotherapy with Concurrent Chemotherapy (Followed by Surgery for Selected Patients)
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
0517 - Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases from Lung, Breast and Prostate Cancer
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
0518 - Efficacy of Zometa for the Prevention of Osteoporsis and Associated Fractures in Patients Receiving RT and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer
The DMC noted that the use of placebo in this study is hindering accrual and should be removed and suggested that bone mets be added as an endpoint.
The DMC concluded that there was no need to modify this protocol as a result of unexpected or excessive toxicity, or rate of accrual.
RTOG Closed Phase III Trials: Review of Toxicity
Breast
9804 - Phase III Trial of Observation +/- Tamoxifen vs. RT +/- Tamoxifen for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
GU
9408 - Endocrine Therapy Used as a Cytoreductive and Cytostatic Agent Prior to RT in Good Prognosis Locally Confined Adenocarcinoma of the Prostate
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
9601 - A Phase III Trial of Radiation Therapy With or Without Casodex in Patients With PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
9902 - Androgen Suppression (AS) & RT vs AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
9910 - Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
H&N
0129 - A Phase III Trial Of Concurrent Radiation and Chemotherapy (Followed By Surgery for Residual Primary/N2-3 Nodal Disease) for Advanced Head and Neck Carcinoma
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
0421 - A Phase III Trial For Locally Recurrent, Previously Irradiated Head And Neck Cancer: Concurrent Re-Irradiation And Chemotherapy Versus Chemotherapy Alone
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
Lung
0214 - A Phase III Comparison of Prophylactic Cranial Irradiation versus Observation in Patients with Locally Advanced Non-Small Cell Lung Cancer
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
0412 - Phase III Randomized Trial of Preoperative Chemotherapy versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage IIIA (N2) Non-Small Cell Lung Cancer
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
Symptom Management
0122 - Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
Manuscript has been accepted for this study.
0215 - Treatment of ED in Patients Treated with Neoadjuvant Androgen Suppression and RT for Prostate Cancer: Impact on Patient and Partner QOL
The DMC concluded that there were no unexpected or excessive toxicity issues for this study.
The DMC voiced concern about continuing the follow-up for closed studies that have not met their target accrual, such as 0412, 0421, and 9902. There should be an assessment of the possible benefit to continued follow-up and earlier termination for those studies with poor statistical power. Response from RTOG Statisticians: follow-up is continued for a minimum of 1 year to assess toxicity for all studies that are closed early due to not meeting targeted accrual. Follow-up on these studies may be longer, depending on the number of patients accrued, if it is determined that there will be sufficient statistical power to analyze some of the protocol endpoints, but this is discussed with the DMC.
The next DMC meeting is scheduled for:
Thursday, June 19, 2008.
9:00 am to 2:00 pm
ACR/RTOG Headquarters
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Allison Martin, M.D. (Ex Officio) (via telephone)
Ann O'Mara, Ph.D., R.N. (Ex Officio) (via telephone)
Kate Murphy
Kenneth E Rosenzweig, M.D.
Elin Sigurdson, M.D.
Nagalingam Suntharalingam, Ph.D.
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Mitchell Machtay, M.D
Ramses Sadek, Ph.D.
Kathryn Winter, M.S.
Thomas J. Wudarski, M.S.
Via Telephone:
Elizabeth Gore, M.D.
Absent:
Marie Diener-West
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Special Reports for Accrual Issues
Lung
RTOG 0214, A Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer
Kathryn Winter, M.S. presented a summary of the accrual for the study. RTOG 0214 was activated September 19, 2002. Target accrual is 1058 and accrual was projected to be 29 cases per month. As of May 23, 2007, 322 patients had been entered, 295 of which are eligible or pending determination of eligibility.
In January 2007, the DMC set the following accrual targets: 12 cases per month by the end of June 2007 and 15 per month by January 2008. The 2007 average monthly accrual through May 23rd has decreased from 8.8 patients to 5.8 cases. At this rate it will take over ten (10) years to reach the target accrual. The RTOG recommended that the study be closed to accrual and that the patients on study should be followed for two years in concert with the primary end point.
The DMC concurred with the Group's recommendation.
Genitourinary
RTOG 0232, A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma
Kathryn Winter, M.S. presented a summary of the accrual for the study. RTOG 0232 was activated on June 11, 2003. Target accrual is 1520 and accrual was projected to be 23.5 per month. As of April 1, 2007, 275 patients had been entered.
In January 2006, the DMC set a monthly accrual target of 12 cases per month by the end of 2006. The average monthly accrual is 6.0 cases per month and 8.0 for the last six months. In At the January 2007 DMC meeting, the committee unanimously recommended that that the study be closed since the average monthly accrual was significantly below the target set by the DMC.
The RTOG Group Chair with the support of the Chairman of the Genitourinary Cancer Committee and the RTOG 0232 Study Chairs appealed the recommendation of the DMC and requested that the study remain open (A copy of the appeal letter is attached.) The RTOG DMC approved the appeal by a majority vote via e-mail in Spring of 2007 and allowed the study to remain open. That decision was reiterated at the meeting.
The Group Chair indicated that a revised protocol will be submitted to CTEP by the end of July 2007. This revision will include a change in the primary endpoint, which would reduce the target accrual to 660 patients and allow the accrual to be completed within 4 years from now.
The RTOG Group Chair concurred with the DMC's recommendations for RTOG 0232.
RTOG Open Phase III Trials: Accrual and Toxicity Reviews
Brain
0320 - WBRT +SRS vs. WBRT + SRS + Temozolomide and WBRT + SRS + Erlotnib in Patients with NSCLC and 1-3 Brain Metastases
0525 - Conventional Adjuvant Temozolomide vs. Dose-Intensive Temozolomide in Patients with Newly Diagnosed Glioblastoma
Kathryn Winter, M.S. informed the DMC that the protocol assumed that approximately 10% of patients that start the induction treatment will not go on to be randomized. This rate is actually closer to 30%. The statistical section is being amended to increase the sample size to 1153 in order to account for this. Fortunately, since the study is accruing at a much higher than projected rate (projected: 20/mth; last 6 mths: 36/mth), the study, at the higher sample size, will meet the targeted accrual a year sooner than the original design.
H&N
0522 - CRT+/- C225for Advanced H&N Cancer
GU
0126 - High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
0232 - A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma
0415 - Hypofractionated 3D-CRT/IMRT vs. Conventionally Fractionated 3D-CRT/IMRT in Patients with Favorable-Risk Prostate Cancer
0521 - A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs. AS and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Predeisone for Localized, High-Risk Prostate Cancer
Dr. Suntharalingam questioned why there was no information on radiation therapy reviews for advanced technology studies where the data is collected at the Image Guided Therapy Center. Kathryn Winter, M.S. stated that she would follow-up on this and that the information would be included in the summary reports for the next semi-annual meeting.
Symptom Management
0435 - A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin for the Reduction of Oral Mucositis in Patients with Locally Advanced Head and Neck Cancer Receiving Radiotherapy with Concurrent Chemotherapy (Followed by Surgery for Selected Patients)
0517 - Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases from Lung, Breast and Prostate Cancer
0518 - Efficacy of Zometa for the Prevention of Osteoporsis and Associated Fractures in Patients Receiving RT and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer
The DMC concluded that there was no need to modify any of these protocols as a result of unexpected or excessive toxicity. The DMC expressed their concern about the accrual to date for RTOG 0320, 435, 517, and 518. The Group Chair indicated that the respective committees will be focusing on these 4 studies at the upcoming RTOG semi-annual meeting to determine if there are any impediments to accrual that can be addressed by the Group. The DMC stated that following the RTOG semi-annual meeting, RTOG should set some accrual targets for these studies for evaluation at the next DMC meeting in January 2008.
RTOG Closed Phase III Trials: Review of Toxicity
Brain
9813 - A Phase III (Phase I Closed) Randomized Study Of Radiation Therapy And Temozolomide (IND #60,265) Versus Radiation Therapy And Nitrosourea For Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
Kathryn Winter, M.S. informed the DMC that RTOG 9813 closed on 3/30/07 due to not meeting targeted accrual. The statistical section is being amended to reflect the change in power that will be available to detect the hypothesized increase in overall survival with the smaller than originally designed sample size.
Breast
9804 - Phase III Trial of Observation +/- Tamoxifen vs. RT +/- Tamoxifen for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
GU
9408 - Endocrine Therapy Used as a Cytoreductive and Cytostatic Agent Prior to RT in Good Prognosis Locally Confined Adenocarcinoma of the Prostate
9601 - A Phase III Trial of Radiation Therapy With or Without Casodex in Patients With PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
9902 - Androgen Suppression (AS) & RT vs AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
9910 - Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
H&N
0129 - A Phase III Trial Of Concurrent Radiation and Chemotherapy (Followed By Surgery for Residual Primary/N2-3 Nodal Disease) for Advanced Head and Neck Carcinoma
0421 - A Phase III Trial For Locally Recurrent, Previously Irradiated Head And Neck Cancer: Concurrent Re-Irradiation And Chemotherapy Versus Chemotherapy Alone
Lung
0412 - Phase III Randomized Trial of Preoperative Chemotherapy versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage IIIA (N2) Non-Small Cell Lung Cancer
Symptom Management
0122 - Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
0215 - Treatment of ED in Patients Treated with Neoadjuvant Androgen Suppression and RT for Prostate Cancer: Impact on Patient and Partner QOL
The DMC concluded that there were no unexpected or excessive toxicity issues for these studies.
The next DMC meeting is scheduled for:
Wednesday January 9, 2008 or Friday, January 11, 2008.
9:00 am to 2:00 pm
ACR/RTOG Headquarters
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Allison Martin, M.D. (Ex Officio) (via telephone)
Ann O'Mara, Ph.D., R.N. (Ex Officio) (via telephone)
Kate Murphy
Elin Sigurdson, M.D.
Nagalingam Suntharalingam, Ph.D.
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Kyounghwa Bae, Ph.D.
Mitchell Machtay, M.D
Thomas F. Pajak, Ph.D.
Kathryn Winter, M.S.
Thomas J. Wudarski, M.S.
Via Telephone:
Kian Ang, M.D.
William U. Shipley, M.D.
Howard Sandler, M.D.
Elizabeth Gore, M.D.
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PLANNED INTERIM ANALYSIS
Head & Neck
RTOG 0129, A Phase III Trial of Concurrent Radiation and Chemotherapy (Followed By Surgery for Residual Primary/N2-3 Nodal Disease) for Advanced Head and Neck Carcinoma
Thomas F. Pajak, Ph.D.. presented the first of two planned interim analysis of the primary endpoint per the statistical analysis plan in the protocol. The study was activated on July 30, 2002. The study sample size was 720 and the total patients entered was 743, as of the date the study closed, June 23, 2005. At the time of this analysis 184 deaths have occurred out of the 724 evaluable patients.
The analysis indicated that the test statistic and p-value both fall into the range where neither the null nor the alternative hypotheses are rejected, therefore the recommendation is that the study should not be reported early and that it should continue as described in the protocol. The second interim analysis will be conducted when 369 deaths have been reported and the final analysis will occur when 553 deaths have been reported.
The DMC concurred with Dr. Pajak's recommendation not to report at this time.
The Group Chair concurred with this recommendation.
Genitourinary
RTOG 9601, A Phase III Trial of Radiation Therapy With or Without Casodex in Patients With PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
Kyounghwa Bae, Ph.D. presented the first of three planned interim analysis of the primary endpoint per the statistical analysis plan in the protocol. The study was activated on March 17, 1998 and closed, March 7, 2003. The study sample size was 810 and the total patients entered was 840. At the time of this first interim analysis 50 deaths have occurred out of the 782 evaluable patients. The second planned analysis of the primary endpoint will occur when 110 deaths are observed.
It is the recommendation not to report the study at this time and that it should continue as described in the protocol. The p-value is not less than the nominal significance level of 0.0001; therefore the current data do not indicate a statistically significant difference in overall survival between the study arms.
The DMC concurred with Dr. Bae's recommendation not to report at this time.
The Group Chair concurred with this recommendation.
SPECIAL REPORTS FOR ACCRUAL ISSUES
Genitourinary
RTOG 0232, A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma
Kyounghwa Bae, Ph.D. presented a summary of the accrual for the study. RTOG 0232 was activated on June 11, 2003. Target accrual is 1520 and accrual was projected to be 23.5 per month. As of December 20, 2006, 246 patients had been entered.
In January 2006, the DMC set a monthly accrual target of 12 cases per month by the end of 2006. The average monthly accrual for 2006 was 6.6 cases per month. This study remains a high priority for the RTOG and it is the only Phase III national trial involving prostate brachytherapy.
The DMC unanimously recommended that that the study be closed since the average monthly accrual was significantly below the target set by the DMC.
The RTOG Group Chair concurred with the DMC's recommendations for RTOG 0232.
Lung
0214 - A Phase III Comparison of Prophylactic Cranial Irradiation vs. Observation in Patients with Locally Advanced NSCLC
Kathryn Winter, M.S. presented a summary of the accrual for the study. RTOG 0214 was activated September 19, 2002. Target accrual is 1058 and accrual was projected to be 29 cases per month. As of December 20, 2006, 294 patients had been entered.
In June 2006, the DMC set the following accrual targets: 12 cases per month by the end of 2006 and 15 per month by June 2007. The 2006 average accrual through December 20th is 9.1 cases. Although this did not meet the target of 12 cases per month, the study has shown a steady increase in the average monthly accrual. A special initiative was undertaken by the Recruitment Working Group to survey the member site and determine what interventions can be made to increase accrual. The study is unique and the endpoint remains a relevant scientific question.
The DMC recommended that the study remain open and that the following revised accrual targets should be imposed: twelve (12) cases per month by the end of June 2007 with an increase to fifteen (15) cases per month by the end of 2007.
The RTOG Group Chair concurred with the DMC's recommendations for RTOG 0214.
RTOG OPEN PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
9813 - RT + Temozolomide vs. RT and BCNU for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
0320 - WBRT +SRS vs. WBRT + SRS + Temozolomide and WBRT + SRS + Erlotnib in Patients with NSCLC and 1-3 Brain Metastases
0525 - Conventional Adjuvant Temozolomide vs. Dose-Intensive Temozolomide in Patients with Newly Diagnosed Glioblastoma
H&N
0421 - Concurrent Re-Irradiation and Chemotherapy versus Chemotherapy Alone for Locally Recurrent, Previously Irradiated Head and Neck Cancer
0522 - CRT+/- C225for Advanced H&N Cancer
GU
0126 - High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
0415 - Hypofractionated 3D-CRT/IMRT vs. Conventionally Fractionated 3D-CRT/IMRT in Patients with Favorable-Risk Prostate Cancer
0521 - A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs. AS and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Predeisone for Localized, High-Risk Prostate Cancer
CCOP
0435 - A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin for the Reduction of Oral Mucositis in Patients with Locally Advanced Head and Neck Cancer Receiving Radiotherapy with Concurrent Chemotherapy (Followed by Surgery for Selected Patients)
0517 - Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases from Lung, Breast and Prostate Cancer
0518 - Efficacy of Zometa for the Prevention of Osteoporsis and Associated Fractures in Patients Receiving RT and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer
The DMC concluded that there was no need to modify any of these protocols as a result of unexpected or excessive toxicity. The DMC expressed their concern about the accrual to date for RTOG 9813 and 0320.
RTOG CLOSED PHASE III TRIALS: REVIEW OF TOXICITY
Breast
9804 - Phase III Trial of Observation +/- Tamoxifen vs. RT +/- Tamoxifen for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
GU
9408 - Endocrine Therapy Used as a Cytoreductive and Cytostatic Agent Prior to RT in Good Prognosis Locally Confined Adenocarcinoma of the Prostate
9902 - Androgen Suppression (AS) & RT vs AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
9910 - Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
Lung
0412 - Phase III Randomized Trial of Preoperative Chemotherapy versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage IIIA (N2) Non-Small Cell Lung Cancer
CCOP
0122 - Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
0215 - Treatment of ED in Patients Treated with Neoadjuvant Androgen Suppression and RT for Prostate Cancer: Impact on Patient and Partner QOL
0315 - A Randomized, Double Blind, Placebo-Controlled Phase III Study to Determine the Efficacy of Sandostatin LAR® Depot (Octreotide Acetate) in Preventing or Reducing the Severity of Chemoradiation-Induced Diarrhea in Patients with Anal or Rectal Cancer
The DMC concluded that there were no unexpected or excessive toxicity issues for these studies.
The next DMC meeting is scheduled for:
Friday June 15, 2007
9:00 am to 2:00 pm
ACR/RTOG Headquarters
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Allison Martin, M.D. (Ex Officio) (via telephone)
Ann O'Mara, Ph.D., R.N. (Ex Officio) (via telephone)
Kenneth Rosenzweig, M.D.
Nagalingam Suntharalingam, Ph.D.
R. Suzanne Swann, Ph.D. (Ex Officio)
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Mitchell Machtay, M.D.
Kathryn Winter, M.S.
Thomas J. Wudarski, M.S
Via Telephone:
Deborah Bruner, Ph.D.
Elizabeth Gore, M.D.
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PLANNED INTERIM ANALYSIS
CCOP
0315 - A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED PHASE III STUDY TO DETERMINE THE EFFICACY OF SANDOSTATIN LAR® DEPOT (OCTREOTIDE ACETATE) IN PREVENTING OR REDUCING THE SEVERITY OF CHEMORADIATION-INDUCED DIARRHEA IN PATIENTS WITH ANAL OR RECTAL CANCER (Study Chairs: Babu Zachariah, M.D., Jaffer Ajani, M.D., Clement Gwede, Ph.D., R.N., Lisa Chin, M.P.H., J.D.)
Kathryn Winter M.S. presented the second planned interim analysis of the primary endpoint per the statistical analysis plan in the protocol. The study was activated on December 5, 2003. The study sample size was 226 and the patient accrual was 233, as of the date the study closed, 2/24/2006. The analysis indicated that the current data do not indicate a statistically significant reduction in grade 2+ diarrhea, therefore the recommendation is that the study should not be reported at this time. Final analysis will occur when all patients have been followed for a minimum of three months.
The DMC concurred with Ms. Winter's recommendation not to report at this time.
The Group Chair concurred with this recommendation.
SPECIAL REPORTS FOR ACCRUAL ISSUES
Breast
9804 - Phase III of Observation +/_ Tamoxifen vs. RT +/- Tamoxifen for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
The DMC recommended that the study close since the accrual targets set at the January 2006 DMC meeting were not met. Follow-up for patients should continue for six (6) years for safety and toxicity related to the administration of Tamoxifen.
Lung
0214 - A Phase III Comparison of Prophylactic Cranial Irradiation vs. Observation in Patients with Locally Advanced NSCLC
The DMC recommended that the study remain open and that the following revised accrual targets should be imposed: twelve (12) cases per month by the end of 2006 with an increase to fifteen (15) cases per month by the end of May 2007.
The RTOG Group Chair concurred with the DMC's recommendations for the studies covered by the Special Reports for Accrual Issues.
RTOG OPEN PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
9813 - RT + Temozolomide vs. RT and BCNU for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
0320 - WBRT +SRS vs. WBRT + SRS + Temozolomide and WBRT + SRS + Erlotnib in Patients with NSCLC and 1-3 Brain Metastases
0525 - Conventional Adjuvant Temozolomide vs. Dose-Intensive Temozolomide in Patients with Newly Diagnosed Glioblastoma
H&N
0421 - Concurrent Re-Irradiation and Chemotherapy versus Chemotherapy Alone for Locally Recurrent, Previously Irradiated Head and Neck Cancer
0522 - CRT+/- C225for Advanced H&N Cancer
GU
0126 - High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
0232 - Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy vs. Brachytherapy Alone for Selected Patients with Intermediate-Risk Prostatic Carcinoma
0415 - Hypofractionated 3D-CRT/IMRT vs. Conventionally Fractionated 3D-CRT/IMRT in Patients with Favorable-Risk Prostate Cancer
0521 - A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs. AS and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Predeisone for Localized, High-Risk Prostate Cancer
Lung
0412 - Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage IIIa (N2) Non-Small Cell Lung Cancer
CCOP
0518 - Efficacy of Zometa for the Prevention of Osteoporsis and Associated Fractures in Patients Receiving RT and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate cancer
The DMC concluded that there was no need to modify any of these protocols as a result of unexpected or excessive toxicity. The DMC expressed their concern about the accrual to date for RTOG 0412, 9813, and 0320.
RTOG CLOSED PHASE III TRIALS: REVIEW OF TOXICITY
H&N
9512 - HX vs. STD FX in T2 Squamous Cell Carcinoma of the Vocal Cord
0129 - CRT (SFX vs. AFX-C) for Advanced H&N Cancer
GU
9408 - Endocrine Therapy Used as a Cytoreductive and Cytostatic Agent Prior to RT in Good Prognosis Locally Confined Adenocarcinoma of the Prostate
9601 - RT with or without Casodex in Patients with PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
9902 - Androgen Suppression (AS) & RT vs AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
9910 - Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
CCOP
0122 - Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
0215 - Treatment of ED in Patients Treated with Neoadjuvant Androgen Suppression and RT for Prostate Cancer: Impact on Patient and Partner QOL
The DMC concluded that there were no unexpected or excessive toxicity issues for these studies.
The next DMC meeting is scheduled for:
Wednesday January 17, 2007
9:00 am to 2:00 pm
ACR/RTOG Headquarters
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Ann O'Mara, Ph.D., R.N. (Ex Officio) (via telephone)
Kenneth Rosenzweig, M.D.
Scott Saxman, M.D. (Ex Officio)
Elin Sigurdson, M.D.
Nagalingam Suntharalingam, Ph.D.
R. Suzanne Swann, Ph.D. (Ex Officio)
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Michelle DeSilvio, Ph.D.
Kathryn Winter, M.S.
Thomas J. Wudarski, M.S
Kyounghwa Bae, Ph.D.
Leonard Lucey, Esq.
Mitchell Machtay, M.D.
Via Telephone:
Hak Choy, M.D.
Elizabeth Gore, M.D.
Bradley Prestidge, M.D.
Howard Sandler, M.D.
Babu Zachariah, M.D.
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PLANNED INTERIM ANALYSES
GU
9408 - A PHASE III TRIAL OF THE STUDY OF ENDOCRINE THERAPY USED AS A CYTOREDUCTIVE AND CYTOSTATIC AGENT PRIOR TO RADIATION THERAPY IN GOOD PROGNOSIS LOCALLY CONFINED ADENOCARCINOMA OF THE PROSTATE (Study Chairs: David G. McGowan, M.D., Christopher U. Jones, M.D.)
Kyounghwa Bae, Ph.D., presented the second planned interim analysis of the primary endpoint per the statistical analysis plan in the protocol. The study was activated on October 31, 1994. The study sample size was 1980 and the patient accrual was 2028, as of the date the study closed, 4/30/2001. The analysis indicated that the current data do not show a significant difference in disease-specific survival curves between the arms, therefore the recommendation is that the study should not be reported at this time.
The DMC concurred with Dr. Bae's recommendation not to report at this time.
The Group Chair concurred with this recommendation.
CCOP
0315 - A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED PHASE III STUDY TO DETERMINE THE EFFICACY OF SANDOSTATIN LAR® DEPOT (OCTREOTIDE ACETATE) IN PREVENTING OR REDUCING THE SEVERITY OF CHEMORADIATION-INDUCED DIARRHEA IN PATIENTS WITH ANAL OR RECTAL CANCER (Study Chair: Babu Zachariah)
Michelle DeSilvio, Ph.D. , presented the second planned blinded interim analysis of the primary endpoint per the statistical analysis plan in the protocol. Dr. DeSilvio presented the pre-treatment characteristics, the summary of the patient case status, and the reported toxicity blinded by treatment arm. This study was activated on 12/5/03 and the required sample size is 226. There were 191 patients accrued as of 10/30/05. The projected completion date based on the last six months accrual is February 2006. Based on the protocol specified stopping rules it was the recommendation of Dr. DeSilvio not to stop the study and report at this time, since the data do not indicate a statistically significant reduction in the incidence of grade +2 diarrhea.
The DMC concurred with Dr. DeSilvio's recommendation not to stop accrual and report the study at this time.
The Group Chair concurred with this recommendation.
SPECIAL REPORTS FOR ACCRUAL ISSUES
Breast
9804 - Phase III of Observation +/_ Tamoxifen vs RT +/- Tamoxifen for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
The DMC recommended that the study remain open and that the following accrual targets should be imposed: sixteen (16) cases per month by the end of May 2006 with an average of twelve (12) cases per month during 2006. The DMC will review this study for accrual at the June 2006 DMC meeting.
GU
0232 - Combined External beam radiation and Transperineal Insterstitial Permanent Brachytherapy with Brachytherapy alone for Selected Patients with Intermediate Risk Prostatic Carcinoma
The DMC recommended that the study remain open and that the following accrual targets should be imposed: ten (10) cases per month by the end of May 2006 and 12 cases by the end of calendar year 2006. This study will be subject to a special accrual report at the January 2007 DMC meeting.
CCOP
0215 - Treatment of Erectile Dysfunction in Patients Treated on RTOG 9910 for Prostate cancer: Impact on Patient and partner Quality of Life
The Group Chair informed the DMC that the study will close in February 2006. The DMC concurred with this action.
Lung
0214 - A Phase4 III Comparison of Prophylactic Cranial Irradiation vs Observation in Patients with Locally Advanced NSCLC
The DMC recommended that the study remain open and that the following accrual targets should be imposed: fifteen (15) cases per month by the end of May 2006.
The RTOG Group Chair concurred with the DMC's recommendations for the studies covered by the Special Reports for Accrual Issues.
RTOG OPEN PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
9813 - RT + Temozolomide vs. RT and BCNU for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
0320 - WBRT +SRS vs WBRT + SRS + Temozolomide and WBRT + SRS + Erlotnib in Patients with NSCLC and 1-3 Brain Metastases
H&N
0522 - CRT+/- C225for Advanced H&N Cancer
0421 - Concurrent Re-Irradiation and Chemotherapy versus Chemotherapy Alone for Locally Recurrent, Previously Irradiated Head and Neck Cancer
GU
0126 - High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
0521 - A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs AS and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Predeisone for Localized, High-Risk Prostate Cancer
Lung
0412 - Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage IIIa (N2) Non-Small Cell Lung Cancer
The DMC concluded that there was no need to modify any of these protocols as a result of unexpected or excessive toxicity. The DMC expressed their concern about the accrual to date for RTOG 0412; there were no other accrual issues identified.
RTOG CLOSED PHASE III TRIALS: REVIEW OF TOXICITY
Brain
9802 - Radiation with or without PCV Chemotherapy in Unfavorable Low-Grade Glioma
H&N
9512 - HX vs Std FX in T2 Squamous Cell Carcinoma of the Vocal Cord
0129 - CRT (SFX vs AFX-C) for Advanced H&N Cancer
GI
9704 - Pre & Post CT 5-FU vs Pre & Post CT Gemcitabine for Postoperative Adjuvant Treatment of Resected Pancreatic Adenocarcinoma
9811 - 5-FU, Mitomycin-C and Radiotherapy vs 5-FU, Cisplatin and Radiotherapy for Anal Canal Carcinoma
GU
9910 - Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
9601 - RT with or without Casodex in Patients with PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
9902 - Androgen Suppression (AS) & RT vs AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
CCOP
0122 - Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
The DMC concluded that there were no unexpected or excessive toxicity issues for these studies.
The next DMC meeting is scheduled for June 16, 2006.
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D. (via telephone)
Dorothy Donahue, R.N.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Ann O'Mara, Ph.D., R.N. (Ex Officio) (via telephone)
Kenneth Rosenzweig, M.D.
Scott Saxman, M.D. (Ex Officio)
Elin Sigurdson, M.D
R. Suzanne Swann, Ph.D. (Ex Officio)
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Michelle DeSilvio, Ph.D.
Mitchell Machtay, M.D.
Kathryn Winter, M.S.
Thomas Wudarski, M.S.
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DISCUSSION ITEMS
Ann O'Mara, Ph.D., R.N. from the Division of Cancer Prevention was welcomed as a new Ex-Officio member of the DMC. She participated in this meeting by telephone.
Dr. Suzanne Swann reviewed the recent revision to the RTOG DMC Policies that clarify the procedures for ad hoc requests, from disease site committee chairs and prospective study chairs, for confidential access to interim results to aid in planning future studies. (Copy Attached)
Dr. Suzanne Swann informed the DMC members of the new NCI/CTEP Guidelines for Slow Accruing Studies that are applicable to all randomized Phase III activated after April 1, 2004. (Copy Attached)
AD HOC ANALYSIS REQUEST
Dr. Howard Sandler, Chairman of the RTOG Genitourinary Cancer Committee, submitted a request for an unplanned interim analysis of RTOG 9408, A Phase III Trial Of The Study Of Endocrine Therapy Used As A Cytoreductive And Cytostatic Agent Prior To Radiation Therapy In Good Prognosis Locally Confined Adenocarcinoma Of The Prostate. This early analysis by treatment arm is aimed at seeing if the results observed by Anthony D'Amico, M.D., Ph.D. in a paper published in Journal of the American Medical Association in August 2004 can be confirmed by RTOG 9408.
The DMC recommended that Dr. Sandler be permitted to do an early analysis of the primary endpoint after amending the protocol statistical plan and that the results be released only if they cross the statistical boundaries. The Group Chair concurred with this recommendation.
INTERIM ANALYSES
GI
9811 - A Phase III Randomized Study of 5-Fluorouracil, Mitomycin-C, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy In Carcinoma Of The Anal Canal (Study Chair: Jaffer Ajani)
Kathryn Winter, M.S., presented the second planned interim analysis of the primary endpoint per the statistical analysis plan in the protocol. The study was activated on October 31, 1998. The study sample size is 650 and the patient accrual as of 4/8/05 was 652, with data from 544 patient's data available for analysis. The analysis showed no evidence of efficacy and crossed the statistical boundary for futility.
The DMC concurred with Ms. Winter's recommendation to close the study immediately and report the study results.
The Group Chair concurred with this recommendation.
CCOP
0315 - A Randomized, Double Blind, Placebo-Controlled Phase III Study To Determine The Efficacy Of Sandostatin Lar® Depot (Octreotide Acetate) In Preventing Or Reducing The Severity Of Chemoradiation-Induced Diarrhea In Patients With Anal Or Rectal Cancer (Study Chair: Babu Zachariah)
Dr. Michelle DeSilvio presented the pre-treatment characteristics, the summary of the patient case status, and the reported toxicity blinded by treatment arm. This study was activated on 12/5/03 and the required sample size is 226. There were 121 patients accrued as of 4/8/05. Based on the treatment completion dates of current patients the earliest date for the interim analysis and a recalculation of the sample size would be in the fall of 2005.
The DMC recommended that the Study Chair consider revising the criteria for the primary endpoint from the incidence of grade three diarrhea or greater to the incidence of grade two diarrhea or greater before the interim analysis.
The Group Chair concurred with this recommendation.
RTOG OPEN PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
9813 - RT + Temozolomide vs. RT and BCNU for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
Breast
9804 - Observation +/- Tamoxifen vs. RT+/- Tamoxifen for Good Risk DCIS of the Female Breast
H&N/Sarcoma
0129 - Concurrent Chemoradiation (Standard Fraction RT vs. Hyperfractionated RT) for Advanced Head & Neck Cancer Patients
0421 - Concurrent Re-Irradiation and Chemotherapy versus Chemotherapy Alone for Locally Recurrent, Previously Irradiated Head and Neck Cancer
GU
0126 - High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
0232 - Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostate Carcinoma
CCOP
0215 - Treatment of Erectile Dysfunction in Patients Treated on RTOG 9910 for Prostate Cancer: Impact on Patient and Partner Quality of Life
0315 - A Randomized, Double-Blind, Placebo-Controlled Study to Determine
the Efficacy of Sandostatin LAR® Depot in Preventing or Reducing the
Severity of CRT-Induced Diarrhea in Patients with Anal or Rectal Cancer
Lung
0214 - A Phase III Comparison of Prophylactic Cranial Irradiation versus Observation in Patients with Locally Advanced Non-Small Cell Lung Cancer
0412 - Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage IIIa (N2) Non-Small Cell Lung Cancer
The DMC concluded that there was no need to modify any of these protocols as a result of unexpected or excessive toxicity. No accrual issues for these studies were identified.
RTOG CLOSED PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
9802 - Radiation with or without PCV Chemotherapy in Unfavorable Low-Grade Glioma
H&N
9512 - HX vs Std FX in T2 Squamous Cell Carcinoma of the Vocal Cord
GI
9704 - Pre & Post CT 5-FU vs Pre & Post CT Gemcitabine for Postoperative Adjuvant Treatment of Resected Pancreatic Adenocarcinoma
GU
9910 - Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
9601 - RT with or without Casodex in Patients with PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
9408 - Endocrine Therapy Used as a Cytoreductive and Cytostatic Agent Prior to RT in Good Prognosis Locally Confined Adenocarcinoma of the Prostate
9902 - Androgen Suppression (AS) & RT vs AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
CCOP
0122 - Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
The DMC concluded that there was no need to modify any protocol as a result of unexpected or excessive toxicity.
Tentative date for next DMC Meeting: January 11, 2006
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D. (via telephone)
Dorothy Donahue, R.N.
Boris Freidlin, Ph.D. (Ex Officio)
Gary Hudes, M.D.
Nagalingam Suntharalingam, Ph.D.
Kenneth Rosenzweig, M.D.
Scott Saxman, M.D. (Ex Officio)
Elin Sigurdson, M.D
R. Suzanne Swann, Ph.D. (Ex Officio)
Scott Saxman, M.D. (Ex Officio)
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Beryl McCormick, M.D. (via telephone)
Mitchell Machtay, M.D.
Michelle DeSilvio, Ph.D.
Brian Berkey, M.S.
William Bice, Ph.D. (via telephone)
Kathryn Winter, M.S.
Kenneth Pienta, M.D. (via telephone)
Thomas Wudarski, M.S.
Deborah Watkins Bruner, Ph.D. (via telephone)
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DISCUSSION: TIMELINE FOR ACTING ON DMC RECOMMENDATIONS
The procedure for the publication of the DMC minutes requires that the RTOG Group Chair and the DMC Chair review and approve them prior to distribution. The DMC recognizes that when a patient safety issue arises there should be no delay in any required actions. The DMC recommends that Group Chair and Group Statistician review the circumstances surrounding any safety issue, prepare the necessary communication or broadcast, and present these materials to the DMC Chair for final approval expeditiously.
SPECIAL ACCRUAL REPORTS
Breast
9804 – Phase III Trial of Observation +/- Tamoxifen vs. RT +/- Tamoxifen for Good Risk Duct Carcinoma In-situ (DCIS) of the Female Breast
(Study Chair: Beryl McCormick)
The DMC recommends that the study continue and that the RTOG vigorously pursue participation by the NSABP and other groups, including international research groups. A monthly target accrual of 12 women per month by December 2005 was recommended and the DMC will review accrual at the January 2006 meeting.
The DMC concluded that there was no need to modify the protocol as a result of unexpected or excessive toxicity.
The Group Chair concurred with this recommendation.
GU
0232 – A Phase III Study Comparing Combined External Beam Radiation And Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone For Selected Patients With Intermediate Risk Prostatic Carcinoma
(Study Chair: Bradley R. Prestidge)
The DMC recommended that the study remain open and that the RTOG take a more aggressive approach in preparing sites for the credentialing process. The DMC established an accrual target of 10 men per month by December 2005 and trial accrual will be assessed at the January 2006 meeting.
The DMC concluded that there was no need to modify the protocol as a result of unexpected or excessive toxicity.
The Group Chair concurred with this recommendation.
0014 – A Phase III Randomized Study of Patients with High Risk, Hormone-Naïve Prostate Cancer: Androgen Blockade with 4 Cycles of Immediate Chemotherapy Versus Androgen Blockade with Delayed Chemotherapy
(Study Chair: Kenneth James Pienta)
The Group Chair stated that this study will be closed due to poor patient accrual.
The DMC concurred with this action.
0215 – Treatment of Erectile Dysfunction in Patients Treated on RTOG 99-10 for Prostate Cancer:Impact on Patient and Partner Quality of Life
(Study Chair: Deborah Watkins Bruner)
The DMC recommended that this study remain open and recommended a monthly accrual target of six men per month by December 2005, which will be assessed at the January 2006 DMC meeting. The DMC also recommended that the eligibility for the study be expanded beyond patients completing treatment on RTOG 9910, and that other agents be added.
The Group Chair concurred with this recommendation.
Lung
0214 – A Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer
(Study Chair: Elizabeth Gore)
The DMC recommended that this study remain open and established a monthly accrual target of 12 patients per month by December 2005, an objective which will be assessed at the January 2006 DMC meeting. The DMC also recommended that the RTOG explore participation by international sites to enhance accrual, including centers and research groups in Japan.
The DMC concluded that there was no need to modify the protocol as a result of unexpected or excessive toxicity.
The Group Chair concurred with this recommendation.
RTOG PHASE III TRIAL - DMC INTERIM ANALYSIS REVIEW
Brain
9802 – A Phase II Study of Observation in Favorable Low-Grade Glioma and A Phase III Study of Radiation with or without PCV Chemotherapy in Unfavorable Low-Grade Glioma
(Study Chair: Edward G. Shaw)
Brian Berkey, M.S., presented the planned interim analysis of the primary endpoint per the analysis plan in the protocol. Dr. Edward was available via telephone for the limited discussion. The study was activated on October 31, 1998 and closed to accrual on June 27, 2002. The study sample size is 252 and the patient accrual was 370.
The DMC concurred with Mr. Berkey’s recommendation to report the primary endpoint of the study now based on the results of the planned interim analysis.
The Group Chair concurred with this recommendation.
RTOG OPEN PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
9813 – RT + Temozolomide vs. RT and BCNU for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
H&N/Sarcoma
0129 – Concurrent Chemoradiation (Standard Fraction RT vs. Hyperfractionated RT) for Advanced Head & Neck Cancer Patients
GI
9811 – 5-Fluorouracil & Mitomycin-C + RT vs. 5-Fluorouracil & Cisplatin + RT in Carcinoma of the Anal Canal
GU
0126 – High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cancer
CCOP
0315 – A Randomized, Double-Blind, Placebo-Controlled Study to Determine
the Efficacy of Sandostatin LAR® Depot in Preventing or Reducing the
Severity of CRT-Induced Diarrhea in Patients with Anal or Rectal Cancer
The DMC concluded that there was no need to modify any of these protocols as a result of unexpected or excessive toxicity. Accrual for these studies is on target.
RTOG CLOSED PHASE III TRIALS: ACCRUAL AND TOXICITY REVIEWS
Brain
0118 – Conventional RT + Thalidomide (NSC# 66847) vs. Conventional RT for Multiple Brain Metastases
H&N
9512 – Hyperfractionated RT vs. Standard Fraction RT in T2 Squamous Cell Carcinoma of the Vocal Cord
GI
9704 – Pre & Post Chemoradiation 5-FU vs. Pre & Post Chemoradiation Gemcitabine for Postoperative Adjuvant Treatment of Resected Pancreatic Adenocarcinoma
GU
9910 – Duration of Neoadjuvant Total Androgen Suppression (TAS) + RT in Intermediate Risk Prostate Cancer
9601 – RT with or without Casodex in Patients with PSA Elevation Following Radical Prostatectomy for pT3N0 Carcinoma of the Prostate
9408 – Endocrine Therapy Used as a Cytoreductive and Cytostatic Agent Prior to RT in Good Prognosis Locally Confined Adenocarcinoma of the Prostate
9902 – Androgen Suppression (AS) & RT vs. AS & RT followed by CT with Paclitaxel, Estramustine, & Etoposide (TEE) for Localized High-Risk Prostate Cancer
CCOP
0122 – Double Blind Study of Nutritional Intervention for Cancer Cachexia Using JUVEN® Nutritional Supplement
The DMC concluded that there was no need to modify any protocol as a result of unexpected or excessive toxicity.
Tentative date for next DMC Meeting: June 8, 2005
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| RTOG Committee Members: | Other attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D. (via telephone)
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Kenneth Rosenzweig, M.D.
Scott Saxman, M.D. (Ex Officio)
Elin Sigurdson, M.D.
R. Suzanne Swann, Ph.D. (Ex Officio)
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Jonathan Knisley, M.D. (via telephone)
Mitchell Machtay, M.D.
Thomas F. Pajak, Ph.D.
Wendy Seiferheld, M.S.
Andy Trotti, M.D. (via telephone)
Kathryn Winter, M.S.
Thomas Wudarski, M.S.
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The RTOG Data Monitoring Committee Policies were revised at the request of the NCI. This was the first meeting conducted under the new policies. Materials were sent to the committee member in advance of the meeting within the time frame specified in the policies. During the initial phase of the meeting each study was presented with the PI present or on the telephone. The PI was excused, and the remainder of the study data was presented. The DMC then met in closed session for each study and formulated its recommendations. The following is a synopsis of the results of the DMC meeting.
PLANNED INTERIM ANALYSIS
RTOG 0118, A PHASE III STUDY OF CONVENTIONAL RADIATION THERAPY PLUS THALIDOMIDE (NSC#66847) VERSUS CONVENTIONAL RADIATION THERAPY FOR MULTIPLE BRAIN METASTASES
Wendy Seiferheld, M.S., presented the planned interim analysis of the primary endpoint per the analysis plan in the protocol. Dr Jonathan Knisley, M.D., the study chair, was also available for the limited discussion via telephone. The study was activated on February 28, 2004. The study sample size is 332 and the patient accrual through April 16, 2004 was 168.
The interim analysis plan allows early stopping for efficacy or for no evidence of efficacy. The interim analysis reported conditional power <0.01 below the cut off for no evidence of efficacy. The DMC recommended stopping the study. The Group Chair concurred with this recommendation.
RTOG 9512, A RANDOMIZED STUDY OF HYPERFRACTIONATION VERSUS CONVENTIONAL FRACTIONATION IN T2 SQUAMOUS CELL CARCINOMA OF THE VOCAL CORD
Thomas F. Pajak, Ph.D., presented the second planned interim analysis of the primary endpoint per the analysis plan in the protocol. Dr Andy Trotti, M.D., the study chair, was also available for the limited discussion via telephone. The study was activated on April 1, 1996 and closed to accrual July 22, 2003. The study sample size was 240 and patient accrual was 250.
The DMC recommended that the analysis and reporting of the study should be completed as planned based on the results of the planned interim analysis. The Group Chair concurred with this recommendation.
RTOG 9811, A PHASE III RANDOMIZED STUDY OF 5-FLUOROURACIL, MITOMYCIN-C, AND RADIOTHERAPY VERSUS 5-FLUOROURACIL, CISPLATIN AND RADIOTHERAPY IN CARCINOMA OF THE ANAL CANAL
Kathryn Winter, M.S., presented the planned interim analysis of the primary endpoint per the analysis plan in the protocol. No study chair was present for the limited discussion. The study was activated on October 31, 1998. The study sample size is 650 and the patient accrual through April 16, 2004 was 537.
The DMC recommended that the study continue on as planned since the current data do not indicate a highly significant difference between the arms or a lack of evidence for a difference and the toxicity profiles compare favorably. The Group Chair concurred with this recommendation.
RTOG OPEN PHASE III TRIALS
R. Suzanne Swann, Ph.D. reviewed accrual and toxicity data for all the other open RTOG Phase III trials:
| Study |
Description |
| 9804 | Breast: DCIS |
| 9813 | Brain: Ana. Astro. (Phase I/III) |
| 9902 | Prostate: High Risk |
| 0014 | Prostate: Advanced Hormone Naive |
| 0122 | Cancer Cachexia/CCOP |
| 0126 | Prostate: 3D |
| 0129 | H&N: Stage III/IV |
| 0214 | Lung: PCI for NSCC |
| 0215 | Erectile Dysfunction/CCOP |
| 0232 | Prostate: Brachytherapy +/- Ext RT |
| 0315 | Anal/Rectal/Sandostatin |
The DMC concluded that there was no need to modify any protocol as a result of unexpected or excessive toxicity. Accrual for these studies is on target except where noted.
The following studies will be formally reviewed by the DMC in January 2005 to assess accrual. Monthly accrual targets are listed below:
RTOG 9804 Breast: DCIS
Accrual target for 2004, twelve (12) patients per month by December 2004
RTOG 9902 Prostate: High Risk
Accrual target for 2004: ten (10) patients per month by December 2004
RTOG 0014 Prostate: Advanced Hormone Naive
Accrual target for 2004: ten (10) patients per month by December 2004
RTOG 0214 Lung: PCI for NSCC
Accrual target for 2004: ten (10) patients per month by December
RTOG 0215 Erectile Dysfunction/CCOP
The DMC reviewed the eligible patient population from RTOG 9910 at this meeting and concluded that there was a sufficient number to complete the study.
RTOG 0232 Prostate: Brachytherapy +/- Ext RT
Accrual has been below the projected monthly accrual.
RTOG CLOSED PHASE III TRIALS
R. Suzanne Swann, Ph.D. reviewed the toxicity summary data for all the closed RTOG Phase III trials:
| Study |
Description |
| 9408 | Prostate Cancer: Early Stage |
| 9601 | Prostatectomy: Casodex |
| 9704 | Pancreas: Resected |
| 9802 | Low Grade Glioma |
| 9910 | Prostate: TAS |
The next DMC meeting is scheduled for January 12, 2005. June 8th was identified as a tentative date for the second on-site meeting in 2005.
The meeting was adjourned.
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| RTOG Committee Members: | Other Attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D. (via telephone)
Dorthy Donahue, R.N.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Gary Hudes, M.D.
Scott Saxman, M.D. (Ex Officio via telephone)
Elin Sigurdson, M.D.
Suzanne R. Swann, Ph.D. (Ex Officio)
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Michelle DeSilvio, Ph.D.
Beryl McCormick, M.D. (via telephone)
Thomas F. Pajak, Ph.D.
Howard M. Sandler, M.D. (via telephone)
Wendy Seiferheld, M.S.
Edward G. Shaw, M.D. (via telephone)
Richard K. Valcenti, M.D. (via telephone)
Kathryn Winter, M.S.
Thomas Wudarski, M.S.
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OPENING REMARKS
Dr. Curran noted that RTOG Leadership recently revised the DMC Policy and distributed a draft of these revisions to the members of the committee for comment. These revisions resulted in part from a meeting on November 7, 2003 between CTEP and RTOG Leadership. Comments should be sent to Thomas Wudarski at RTOG Headquarters. A final draft incorporating all edit/comments will be distributed to the DMC members in approximately thirty (30) days.
The timing for the distribution of material prior to the meeting has been adjusted so that DMC members will have two (2) full weeks to review the material and prepare for the meeting.
Dr. Curran welcomed the new members of the Committee: Gary Hudes, M.D., Fox Chase Cancer Center, who is a medical oncologist, Kenneth Rosenzweig, M.D., Memorial Sloan Kettering Cancer Center, a radiation oncologist and Nagalingam Suntharalingam, Ph.D., a medical physicist.
FULL REVIEW
RTOG 98-02, A PHASE II STUDY OF OBSERVATION IN FAVORABLE LOW-GRADE GLIOMA AND A PHASE III STUDY OF RADIATION WITH OR WITHOUT PCV CHEMOTHERAPY IN UNFAVORABLE LOW-GRADE GLIOMA
Wendy Seiferheld, M.S., presented the second planned interim analysis of the primary endpoints per protocol analysis plan in the study. It was activated on October 31, 1998 and closed to accrual June 27, 2002. The DMC recommended that the study continue according to the protocol. The Group Chair concurred with this recommendation.
REVIEW OF RTOG STUDIES WITH ACCRUAL TARGETS ESTABLISHED AT LAST DMC MEETING, JUNE 18, 2003
RTOG 9804, PHASE III TRIAL OF OBSERVATION +/- TAMOXIFEN VS. RT +/- TAMOXIFEN FOR GOOD RISK DUCT CARCINOMA IN-SITU (DCIS) OF THE FEMALE BREAST
Kathryn Winter, M.S., presented accrual data for the study and the Study Chair, Dr. Beryl McCormick responded to questions from the Committee. The target established at the last DMC meeting was 400 patients by December 31, 2003; actual accrual at that date was 373.
The DMC acknowledged that the question posed by this study is still valid and that the accrual rate has shown improvement. The DMC recommends that the study continue with careful monitoring of the accrual. A new target accrual rate was established: twelve (12) patients per month by December 2004.
The DMC went on to suggest to the Study Chair that the eligibility could be changed to increase accrual. In addition, they suggested that the effect of slower-than-projected accrual on the statistics section should be evaluated.
RTOG 99-02, A PHASE III PROTOCOL OF ANDROGEN SUPPRESSION (AS) AND RADIATION THERAPY (RT) VS AS AND RT FOLLOWED BY CHEMOTHERAPY WITH PACLITAXEL, ESTRAMUSTINE, AND ETOPOSIDE (TEE) FOR LOCALIZED, HIGH-RISK, PROSTATE CANCER
Michelle DeSilvio, Ph.D., presented the accrual data and the Study Chair, Dr. Howard Sandler responded to questions from the Committee. The target established at the last DMC meeting was 396 patients as of December 31, 2003; actual accrual at that date was 345.
The DMC acknowledged that the question posed by this study is still valid and that the accrual was close to target. The DMC recommends that the study continue with careful monitoring of the accrual due to their concern about time to completion of the study. A new target was established, at least ten (10) patients per month by the end of 2004.
The Committee urged the Study Chair, Dr. Howard Sandler to contact the American Urologic Association and the appropriate advocacy groups to raise the profile of the study and to seek their recommendations regarding how to increase accrual.
The Committee recommended that the Study Chair consider amending the protocol to either change the range of radiation therapy dosage or add more flexibility to the chemotherapy regime.
The proposed revision to the statistical section of the protocol was approved, except that the number of interim analyses cannot be reduced from three in the original design.
RTOG P-0011, PHASE III RANDOMIZED STUDY OF ADJUVANT THERAPY FOR HIGH RISK pT2-3N0 PROSTATE CANCER
Michelle DeSilvio, Ph.D., presented the accrual data and the Study Chair, Dr. Richard Valicenti responded to questions from the Committee. The target established at the last DMC meeting was 75 patients as of December 31, 2003; actual accrual by that date 50. The DMC recommended that this study should be closed.
The Group Chair concurred with the recommendations for these three (3) studies.
OPEN RTOG PHASE III TRIALS
Dr. Pajak reviewed accrual and toxicity data for all the other open RTOG Phase III trials:
| Study |
Description |
| 9804 | Breast: DCIS |
| 9811 | GI: Anal Canal |
| 9813 | Brain: Ana. Astro. (Phase I/III) |
| 9902 | Prostate: High Risk |
| 9910 | Prostate: TAS |
| 0011 | Prostate: High Risk pT3NO |
| 0014 | Prostate: Advanced Hormone Naive |
| 0118 | Thalidomide for Brain Metastases |
| 0122 | Cancer Cachexia/CCOP |
| 0126 | Prostate: 3D |
| 0129 | H&N: Stage III/IV |
| 0214 | Lung: PCI for NSCC |
| 0215 | Erectile Dysfunction/CCOP |
| 0232 | Prostate: Brachytherapy +/- Ext RT |
| 0315 | Anal/Rectal/Sandostatin |
The DMC concluded that there was no need to modify any protocol as a result of unexpected or excessive toxicity. Accrual for these studies is on target except where noted.
Study specific notes:
RTOG 0014 Prostate: Advanced Hormone Naive
Accrual target for 2004: ten (10) patient per month by 12/04
RTOG 0118 Thalidomide for Brain Metastases
DMC requested a report on vascular events at the next meeting
RTOG 0129 H&N: Stage III/IV
Accrual on target; proposed sample size increase approved
RTOG 0214 Lung: PCI for NSCC
Accrual target for 2004: ten (10) patients per month by 12/04
RTOG 0215 Erectile Dysfunction/CCOP
Formal review will be scheduled for June 2004 meeting to determine if the patient population from RTOG 9910 can provide sufficient patients to continue this study
RTOG 0232 Prostate: Brachytherapy +/- Ext RT
DMC requested a review of accrual in June 2004
The next DMC meetings will be scheduled for June 16, 2004 and January 12, 2005.
The meeting was adjourned.
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| RTOG Committee Members: | Other Attendees: |
Joseph Aisner, M.D. Chair
Walter J. Curran, Jr., M.D. (Ex Officio)
Marie Diener-West, Ph.D.
Dorthy Donahue, R.N.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Mitchell Machtay, M.D. (Ex Officio)
Scott Saxman, M.D. (Ex Officio)
Charles B. Scott, Ph.D. (Ex Officio)
Elin Sigurdson, M.D. |
Ross Abrams, M.D.
Brian A. Berkey, M.S.
Michelle DeSilvio, Ph.D.
Leonard Lucey
Thomas F. Pajak, Ph.D.
William F. Regine, M.D.
Suzanne R. Swann, Ph.D.
Kathryn Winter, M.S.
Thomas Wudarski
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RTOG 9704
Dr. Pajak presented accrual, pretreatment characteristics, toxicity data for this trial. It was activated on July 20, 1998 and closed July 26, 2002, and as of this date 538 patients have been accrued. The average monthly accrual was 11.2 cases. This was a protocol-planned analysis The DMC recommended early reporting of toxicity and survival results. The results will be presented to the appropriate committees at the RTOG Semi-Annual Meeting in Montreal, June 2003. The Group Chair concurred with this recommendation.
RTOG 9903
Dr. Pajak presented accrual, pretreatment characteristics, toxicity data for this trial. It was activated on June 30, 2000 and as of this date 129 patients have been accrued. The average monthly accrual is 3.8 cases. There were no toxicity issues identified. The protocol calls for a review of the sample size based on the assumption that, the risk of failure among the patient groups was equal, when 150 patients were entered. The DMC recommended an assessment of the hemoglobin response and requested a power calculation for the local-regional and survival objectives. The Group Chair concurred with this recommendation.
OPEN RTOG PHASE III TRIALS
Dr. Scott reviewed accrual and toxicity data for the following Phase III trials:
| Study |
Description |
| 9512 | H&N: T2 Vocal Cords |
| 9804 | Breast: DCIS |
| 9811 | GI: Anal Canal |
| 9813 | Brain: Ana. Astro. (Phase I/II) |
| 9902 | Prostate: High Risk |
| 9903 | H&N: Anemic Patients |
| 9910 | Prostate: TAS |
| 0011 | Prostate: High Risk pT3NO |
| 0014 | Prostate: Advanced Hormone Naive |
| 0018 | Brain: Thalidomide for Metastases |
| 0122 | Cancer Cachexia/CCOP |
| 0126 | Prostate: 3D |
| 0129 | H&N: Stage III/IV |
| 0214 | Lung: PCI for NSCC |
| 0215 | Erectile Dysfunction/CCOP |
The DMC concluded that there was no need to modify any protocol as a result of unexpected or excessive toxicity.
Study specific notes:
9512 The study will close to accrual July 2003
9804 The DMC set an accrual target to be reached by January 2004, and recommended a hold on a proposed amendment until that time.
9811 Accrual on target
9813 Accrual will be closely monitored since the FDA mandated that the study be completed by the end of 2004.
9902 The DMC set an accrual target to be reached by January 2004, and requested a report on thrombolitic events at next DMC meeting
9903 Patient accrual will be reviewed in January 2004 along with ancillary data requested by the DMC
9910 Accrual on target
0011 The DMC set an accrual target to be reached by January 2004
0014 Will establish accrual target in 2004
0118 DMC requested a report on vascular events at the next meeting
0122 Accrual on target
0126 Will establish accrual target in 2004, IMRT issues pending
0129 Accrual on target
0214 DMC requested a report on the number of IRB approved sites and will establish an accrual target in 2004
0215 Slow accrual noted as well as the change in eligibility criteria.
The DMC discussed the request from a member institution to unblind the treatment regime for a patient on RTOG 9601. The DMC recommended that when a treatment decision needs to be made, the RTOG will authorize the unblinding of the patient treatment regime for this patient. The Group Chair concurred with this recommendation.
The next DMC meeting will be scheduled for February 2004.
The meeting was adjourned.
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Sixteen (16) phase III trials were reviewed for toxicity and patient accrual. There were no toxicity issues for these studies, a summary table of patient accrual is attached.
Attendees: Joseph Aisner, M.D., Elin Sigurdson, M.D., Marie Diener-West, Ph.D., Norman Wolmark, M.D., Walter J. Curran, Jr., M.D., Boris Freidlin, Ph.D., Mitchell Machtay, M.D., Scott Saxman, M.D., Richard S. Kaplan, M.D., Ph.D., Charles Scott, Ph.D.
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| Study |
Description |
Date Opened |
Targeted Accrual |
Total # Entered |
Projected Completion |
| 9512 | H&N: T2 Vocal Cord | 04/96 | 240 | 237 | Mar-03 |
| 9601 | Prostatectomy | 03/98 | 810 | 800 | Feb-03 |
| 9804 | Breast: DCIS | 12/99 | 1790 | 254 | > 2010 |
| 9811 | GI: Anal Canal | 10/98 | 650 | 403 | Aug-05 |
| 9813 | Brain: Ana. Astro. (Phase I/III) | 08/02* Phase III | 454 Phase III | 6 Phase III | Recently re-opened |
| 9902 | Prostate: High Risk | 01/00** | 1220 | 258 | > 2010 |
| 9903 | H&N: Anemic Patients | 06/00 | 372 | 111 | Oct-06 |
| 9905 | GYN: Endometrium | 08/00 | 436 | 45 | > 2010 |
| 9910 | Prostate: TAS | 02/00 | 1540 | 1098 | Summer 2004 |
| 0011 | Prostate: High Risk pT3NO | 07/01 | 1398** | 14 | > 2010 |
| 0014 | Prostate: Advanced Hormone Naive | 10/02 | 1050 | 2 | Recently opened |
| 0118 | Brain: Thalidomide for Metastases | 2/02**** | 332 | 46 | Jun-06 |
| 0126 | Prostate: 3D | 3/02 | 1520 | 47 | > 2010 |
| 0129 | H&N: Stage III/IV | 7/02 | 480 | 50 | Jun-07 |
| 0214 | Lung: PCI for NSCC | 9/02 | 1058 | 3 | Recently opened |
| 0215 | Erectile Dysfunction/CCOP | 1/03 | 332 | 0 | Recently opened |
* Reopened 8/15/02 as a phase III trial
** Reopened 6/03/2002 after accrual was suspended
*** Sample reduced by dropping the hormone only arm
**** Reopened 6/10/2002 after accrual was suspended
Notes: 9902 recommendation that any occurance of DVT be reported to DMC and RTOG membership and establish accrual milestones to monitor slow accrual
9903 awaiting for approval of protocol from Health Canada, should improve accrual
9905 recommendation to close study due to slow accrual
9804 recommendation to establish accrual milestones due to slow accrual
0011 recommendation to establish accrual milestones due to slow accrual
0126 recommendation to establish accrual milestones due to slow accrual
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Attendees
| Committee Members: | RTOG Staff: |
Joseph Aisner, M.D. (Chairman)
Walter Curran, M.D. (Ex Officio)
Marie Diener-West, Ph.D.
Dorthy Donahue, R.N.
Boris Freidlin, Ph.D. (Ex Officio)
Eli Glatstein, M.D.
Thomas Pajak, Ph.D. (Ex Officio)
Scott Saxman, M.D. (Ex Officio) |
Mitchell Machtay, M.D.
Thomas Wudarski |
This DMC meeting was conducted via conference call.
The DMC reviewed the patient accrual (based on June 1, 2002 cutoff) for the following RTOG Phase III Trials:
| Study |
Description |
DMC Recommendation/Comments |
| 9512 | H&N: T2 Vocal Cord | Satisfactory |
| 9601 | Prostatectomy | Satisfactory |
| 9704 | GI:Pancreas | Study Closed |
| 9714 | Bone Metastases/CCOP | Study Closed |
| 9802 | Brain: Low Grade | Study Closed |
| 9804 | Breast: DCIS | Review study in June 2003 to determine effect of ACoSOG participation |
| 9811 | GI: Anal Canal | Satisfactory |
| 9813 | Brain: Ana. Astro (Phase I/III) | Pilot completed; Phase III component to be submitted for NCI approval |
| 9901 | H&N: Mucositis/CCOP | Satisfactory |
| 9902 | Prostate: High Risk | Review accrual in January 2003 to determine effect of the amendment |
| 9903 | H&N: Anemic Patients | Unsatisfactory - amendment pending at NCI to expand allowable chemoradiation programs |
| 9905 | Gyn: Endometrial Cancer | The DMC expressed concern about the accrual even though NCIC has joined the study. Final recommendations are awaiting GOG’s decision on their endometrial cancer study. |
| 9910 | Prostate: TAS | Satisfactory |
| 0011 | Prostate: High Risk pT3NO | The DMC expressed concern about the accrual and recommended discontinuing the hormone only arm. A protocol amendment may be sent be sent to NCI proposing such a change. |
| 0118 | Brain Metastases: Thalidomide | Just Opened |
| 0126 | Prostate: 3D | Just Opened |
The DMC reviewed the toxicity reports (based on June 1, 2002 cutoff) and concluded that there was no need to modify any protocol as a result of excessive toxicity for the following RTOG Phase III Trials:
| Study |
Description |
DMC Recommendation/Comments |
| 9512 | H&N: T2 Vocal Cord | Acceptable |
| 9601 | Prostatectomy | Acceptable / High ineligibility rate noted |
| 9704 | GI: Pancreas | Acceptable |
| 9714 | Bone Mets/CCOP | Acceptable |
| 9802 | Brain: Low Grade | Acceptable |
| 9804 | Breast: DCIS | Acceptable |
| 9811 | GI: Anal Canal | Acceptable |
| 9813 | Brain: Ana. Astro (Phase I/III) | Acceptable |
| 9901 | H&N: Mucositis/CCOP | Acceptable |
| 9902 | Prostate: High Risk | Acceptable |
| 9903 | H&N: Anemic Patients | Acceptable / Recommendation to report rates of deep venous thrombosis (DVT) and pulmonary embolic events separately in the future |
| 9905 | Gyn: Endometrium | Acceptable |
| 9910 | Prostate: TAS | Acceptable / Recommendation to report rates of DVT and pulmonary embolic events separately in the future |
| 0011 | Prostate: High Risk pT3NO | Acceptable |
| 0118 | Brain Metastases: Thalidomide | Just opened / Recommendation to monitor rates of DVT and other vascular events |
| 0126 | Prostate: 3D | Just opened |
The RTOG Data Monitoring Committee and the Group Chair concurred with these findings and recommendations.
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ATTENDEES
| Committee Members: | Study Chairmen: |
| Joseph Aisner, M.D. | Kenneth Pienta, M.D., Medical Oncology |
| Walter Curran, M.D. (Ex Officio) | Howard Sandler, M.D., Radiation Oncology |
| Marie Diener-West, Ph.D. | |
| Dorthy Donahue, R.N. | RTOG Staff: |
| Boris Freidlin, Ph.D. (Ex Officio) | |
| Eli Glatstein, M.D. | Michelle DeSilvio, Ph.D. |
| Albert Jenemann, S.J., Ph.D. | Phyllis Duda, R.N., M.S.N., O.C.N. |
| Thomas Pajak, Ph.D. (Ex Officio) | Linda Kish |
| Scott Saxman, M.D. (Ex Officio) | Beverly Kratzel |
| Norman Wolmark, M.D. | Mitchell Machtay, M.D. |
| Thomas Wudarski |
| This DMC meeting was conducted via conference call. |
RTOG 9902 A PHASE III PROTOCOL OF ANDROGEN SUPPRESSION (AS) AND RADIATION THERAPY (RT) VS AS AND RT FOLLOWED BY CHEMOTHERAPY WITH PACLITAXEL, ESTRAMUSTINE, AND ETOPOSIDE (TEE) FOR LOCALIZED, HIGH-RISK, PROSTATE CANCER
A recent medical oncology review determined that there was a greater than expected number of thromboembolic events in Arm 2, the chemotherapy arm, of this study. The Medical Oncologist reviewed 38 cases that had complete chemotherapy information. There were 7 cases that did not receive any chemotherapy; of the remaining 31 cases, 7 experienced a grade 2 or higher thromboembolic event (23%). This information was reported to the Data Monitoring Committee (DMC) on March 22, 2002. Following this initial report, an additional 7 cases reported a grade 2 or greater thromboembolic event.
The RTOG and the DMC have proposed amendments to this protocol that include increasing the intensity of anticoagulation in the chemotherapy arm. While waiting for the revision to be approved and the protocol re-opened, the following suggestions are made for patients enrolled to 99-02 and randomized to the chemotherapy arm. At this time, all patients should continue to receive androgen suppression and radiation therapy as specified by the protocol.
I. ARM 2 PATIENTS WHO HAVE COMPLETED PROTOCOL CHEMOTHERAPY:
Please inform these patients of the increased incidence of thromboembolic events as discussed above. Continue to observe for incidence of thromboembolic events. Any thromboembolic event (TIA, CVA, MI, DVT, PE) of any grade warrants a phone report to HQ with 48 hours of knowledge that the event occurred.
II. ARM 2 PATIENTS CURRENTLY RECEIVING PROTOCOL CHEMOTHERAPY:
Please inform these patients of the increased incidence of thromboembolic events.
These patients will have the option to:
1) Discontinue chemotherapy.
2) Continued chemotherapy may be an option for selected patients who wish to
do so. If so, before the patient resumes chemotherapy, four requirements
must be met:
a. Treating physician must speak with Dr. Kenneth Pienta, the Medical Oncologist for this protocol.
b. Patient must sign protocol Z1 form. (Will be mailed to you after discussion with Dr. Pienta.)
c. The patient must have no prior history of a thromboembolic event (TIA, CVA, DVT, PE), or a contraindication to Coumadin® (warfarin) therapy.
d. The patient must begin therapeutic Coumadin® (warfarin) with the goal of attaining an INR of >1.5 but < 2.5.
If and when these four conditions are met, the patient may restart chemotherapy. When RTOG 99-02 is re-opened to accrual (with revised consent form), the patient must sign the revised local IRB approved consent form.
**Note: If a patient experiences a thromboembolic event of any grade during protocol chemotherapy, the chemotherapy will be discontinued immediately. If a patient suffers a bleeding event that requires discontinuation of Coumadin® therapy, all chemotherapy will be immediately discontinued.
III. ARM 2 PATIENTS WHO HAVE NOT BEGUN PROTOCOL CHEMOTHERAPY:
Please inform these patients of the increased incidence of thromboembolic events. No protocol chemotherapy will be administered until the following conditions are met:
1) RTOG 99-02 is re-opened to accrual.
2) The amended protocol is approved by your institutional IRB.
3) Enrolled patients are re-consented to the revised protocol.
4) Patients with a history of thromboembolic events (TIA, CVA, DVT, PE) or a
contraindication to Coumadin® (warfarin) therapy will not receive protocol chemotherapy.
The amendment to 99-02 is currently being written and will be forwarded to NCI for their | |
