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Howard Sandler, M.D., Chair
OPEN STUDIES
RTOG 0126 - Dr. Michalski noted accrual remains excellent. This protocol will close in mid 2008. There have been two grade 5 toxicities in patients using anticoagulation and who had other comorbidities.
RTOG 0232/0612 - Dr. Prestidge discussed options for improving accrual. There is some concern accrual will hinder trial completion, but a renewed effort to improve accrual from 8 patients/month to 10 patients/month is anticipated. RTOG 0612 is a companion trial that offers case credit for submitting fresh tissue obtained during the brachytherapy procedure.
RTOG 0233 - Dr. Zietman noted this study continues to accrue 2-3 cases per month and a follow-up concept is in development [see RTOG 0712 below].
RTOG 0415 - Dr. Lee noted this study just open and has accrued over 80 patients. No major issues were raised.
RTOG 0517 - Dr. Seider noted this trial is open and is expected to accrue well as it is a relatively simple phase III CCOP trial.
RTOG 0518 - Dr. Lawton noted this study is open. There is extra funding to support this trial which is well above the usual CCOP rate and there is funding for most of the extra tests required for the study. Currently the trial employs placebo infusions, but this may be dropped.
RTOG 0521 - Dr. Rosenthal noted this study has opened and has more than 80 pts accrued. It is currently accruing at the expected rate. In January alone, 17 patients were enrolled.
RTOG 0524 - Dr. Michaelson noted 12/88 have been accrued. Additional accrual was recommended for this patient population which is common in radiation oncology practices. This study is available through the CTSU.
PENDING STUDIES
AMG-162 - Dr. Roach will discuss with Amgen. This trial may not move ahead.
RTOG 0526 - Dr. Pisansky noted the salvage brachytherapy trial is at CTEP.
RTOG 0534 - Dr. Pollack reviewed this approved "salvage" concept. 3 arms - PB only, PB and STAD, Pelvis/PB and STAD. Protocol has been submitted to CTEP.
RTOG 0621 - Dr. Hurwitz updated the committee on the progress of this trial of chemotherapy for patients with high risk of failure (>50%) after radical prostatectomy.
RTOG 0622 - Dr. Valicenti updated the committee on the progress of this study of samarium using for poor prognosis salvage cases with biochemical failure after radical prostatectomy.
RTOG 0626 - Dr. Zietman noted this proton therapy phase II trial is progressing as a concept and multiple proton sites will be participating.
RTOG 0712 - This is the successor to RTOG 0233. Dr. Coen described the concept which is a randomized phase II design evaluating BID RT chemotherapy with a doublet of adjuvant chemotherapy to QD RT and gemicitabine chemosensitization with the same doublet.
OTHER ISSUES:
Drs. Sartor, Gomella & Pollack updated the group on Medical Oncology, Urology, and GU TRP issues.
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Howard Sandler, M.D., Chair
Dr. Sandler noted Oliver Sartor of Dana Farber Cancer Institute has replaced Dr. Pienta as the Medical Oncology Co-Chair.
OPEN STUDIES:
RTOG 0126 Dr. Michalski noted accrual remains excellent at about 40 cases per month.
RTOG 0415 Dr. Michalski noted this study is just open and has accrued 2 patients. There may be an IGRT registry amendment to be organized by Dr. Kestin.
RTOG 0233 Dr. Zietman noted this study continues to accrue at 2-3 cases per month.
RTOG 0232 Dr. Prestidge discussed options for improving accrual. He will work with RTOG HQ on periodic awareness e-mails and we will explore changing the endpoint to biochemical to reduce the sample size. Also RTOG 0612 a companion trial is open and brings ½ case credit. This study may be broadened to include RTOG 0126/0526]
RTOG 0521 Dr. Rosenthal noted this study has opened and has 17 pts. There was discussion of insurance coverage for docetaxel. Dr. Sartor will investigate further and will serve as a resource for chemotherapy questions on this study. In addition, he will investigate standard chemotherapy orders to help facilitate protocol activation.
RTOG 0524 Dr. Sandler noted 5/88 have been accrued and 4/5 have adequate Her 2 expression, which is encouraging. Insurance issues for MUGA scans were raised, however.
RTOG 0518 Dr. Sandler noted this study is open. There is extra funding to support this trial well above the usual CCOP rate.
PENDING CONCEPTS:
RTOG 0534 Dr. Pollack reviewed this approved salvage concept. 3 arms PB only, PB and STAD, Pelvis/PB and STAD. Protocol should be submitted to CTEP soon.
AMG-162 Dr. Roach will discuss at next RTOG meeting.
HDR Dr. Hsu presented two concepts: Pelvic RT + 9.5 vs. 10.5 Gy HDR and HDR monotherapy vs. LDR monotherapy. The second concept will be submitted to CCOP mechanism (primary endpoint toxicity). The first concept will be revisited at the next meeting.
RTOG 0526 Dr. Pisansky noted the salvage brachytherapy trial is at CTEP.
Sildenafil as ED preventer Concept reviewed. Fox Chase Cancer Center CCOP is coordinating center, but will be open thru RTOG CCOP as well.
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Howard Sandler, M.D., Chair
ACTIVE TRIALS
RTOG 0126 Dr. Michalski presented the current status of the trial. It is accruing at approximately 30 patients per month. At the current accrual rate, it will close in 2008.
RTOG 0233 A randomized Phase II bladder cancer trial continues to accrue at the standard RTOG monthly accrual rate for bladder preservation protocols. Although most of the accrual is from Massachusetts General Hospital, there has been a broadening of accrual for this particular trial. Perhaps this indicates increased interest in RTOG-led bladder preservation studies.
RTOG 0215 This CCOP Viagra study has been significantly modified. Previously patients were eligible only if they had previously participated in RTOG 9910. Now any patients with impotence following neoadjuvant androgen deprivation are allowed. There seems to be considerable interest in the revised study.
RTOG 0232 There was an extensive discussion regarding this brachytherapy study for early and intermediate risk prostate cancer patients. Accrual has been approximately 7 patients per month. Efforts to boost accrual have included publication of a helpful RTOG brochure, allowing IMRT for the external beam portion of the therapy, and considering changing the interval between registration and brachytherapy, given scheduling may occasionally be an issue. Accrual increases for this trial are critical and accrual will be monitoring carefully by the RTOG Data Monitoring Committee.
RTOG 0321 This is an activate HDR brachytherapy trial. It accrued 6 patients in June and is up to 17 total enrollees. Approximately 6 institutions have been accredited and others are encouraged to go thru accreditation process.
ENDORSED STUDIES THRU CTSU
JPR.7 Approximately 30 patients have been accrued thru RTOG. This trial will close in 2005.
PENDING STUDIES
RTOG 0518 Dr. Lawton will be the Principal Investigator for this trial which will investigate bisphosponates to prevent skeletal-related events. Men with prostate cancer who will undergo at least one year of LHRH agonists will be randomized to receive either calcium and vitamin D or calcium and vitamin D intravenous zoledronic acid. This concept has been CTEP-approved and the protocol will be submitted to Washington shortly.
RTOG 0524 This is a trial with Dror Michaelson and Alan Pollack. It will treat patients who are not surgical candidates and who have bladder cancer. They will receive either radiation or concurrent paclitaxel or the same along with Herceptin, depending on the status of HER-2-expression. If HER-2 expression is 3+ or greater, they will receive the combination of Herceptin and Paclitaxel. The protocol document has been submitted to CTEP in a revised form and final approval is expected shortly.
RTOG 0534 Is a concept for salvage radiation following radical prostatectomy. Patients who have a PSA of 0.2 to 4.0 will be randomized to one of 3 arms; either radiation to the prostate bed alone, radiation to the prostate bed along with neoadjuvant and concurrent androgen ablation, or radiation to the whole pelvis followed by a prostate bed boost along with neoadjuvant and concurrent androgen ablation. Statistics will be working on the sample size calculation and it is hoped that this Phase III concept will be submitted to CTEP shortly.
RTOG 0415 Is a hypofractionation concept for low-risk prostatic cancer. The initial concept was rejected by CTEP but revised concept with intensified radiation in both the conventional fractionation arm and the hyperfractionation arm were discussed and will be resubmitted to CTEP shortly. The trial will have a non-inferiority design with the standard arm scheduled to receive a dose of 73.8 Gy in 1.8 Gy fractions and the hypofraction arm a dose of 70 Gy in 28, 2.5 Gy fractions. A non inferiority limit of 7% has been deemed to be acceptable for biochemical failure.
OTHER ISSUES
Dr. Roach discussed the AMG 162 concept which will treat patients who were similar to those in the closed study RTOG 0014. Patients will receive the investigational agent in an effort to reduce skeletal metastasis.
Dr. Berk discussed the CCOP proposals including a proposal for ginseng to reduce cancer fatigue and systemic radiotherapy for patients with skeletal metastic disease.
It is expected a pilot study investigating the feasibility of obtaining fresh tissue from patients undergoing prostate brachytherapy with Dr. Chakarvarti as the PI will open in the near future.
RTOG 0521 Is a successor trial to RTOG 9902. This trial has been approved by patients to RTOG 9202 type treatment, with 2 years of androgen ablation, versus the same type of treatment with 6 cycles of docetaxel and prednisone following radiation therapy. IMRT will be allowed for both the prostate treatment and the whole pelvic portion.
Len Gomella updated the group on the results of SWOG 8794. This trial was presented at the AUA. RTOG has participated in this trial and should be involved in the manuscript.
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Howard Sandler, M.D., Chair
1. ACTIVE TRIALS
RTOG 0014 - This trial is accruing sub-optimally and because of the low accrual rate has been terminated by the Data Monitoring Committee. Thus, two important prostate cancer chemotherapy trials, RTOG 0014 and ECOG 1899 failed to meet their accrual goals and have been closed. This is despite recent evidence indicating chemotherapy may be playing a more important role in hormone refractory prostate cancer.
RTOG 0126 - A Phase III dose study. Accrual continues to be excellent on this trial, which is the best currently accruing GU cancer trial.
RTOG 0215 - This trial continues to accrue patients from RTOG 9910 could have erectile dysfunction. There is some consideration this trial will be expanded to include patients who were not participants in RTOG 9910. In addition, Dr. Bruner is investigating the role of phosphodiesterase type 5 inhibitors in the prevention of erectile dysfunction.
RTOG 0232 - This important randomized brachytherapy trial is accruing steadily, but not quite at the proposed accrual rate. The Committee had a long discussion about potential barriers to enrollment. Dr. Prestidge will submit amendments that allow IMRT for the external beam component in an effort to improve accrual.
RTOG 0233 - This randomized Phase II bladder cancer trial continues to accrue as expected.
RTOG 0321 - Is an activated HDR brachytherapy trial has accrued its first patient.
2. ENDORSED STUDIES THRU CTSU
JPR-7 is accruing well. Approximately 20 patients have been accrued thru the RTOG. It is expected this trial will close in 2005.
3. PENDING STUDIES
RTOG 0521 - Is a successor trial to RTOG 9902. This trial will use chemotherapy (Docetaxel and Prednisone) in patients at high-risk for metastatic disease but with localized prostate cancer. This trial has been reviewed favorably by CTEP.
RTOG 0524 - Is a Phase II trial for non-cystectomy patients with muscle invasive bladder cancer of TUR followed by a combination of Paclitaxel and Trastuzumab with daily irradiation or Paclitaxel with daily irradiation. Although the process has been slow, it is likely this trial will be activated in 2005. It represents a new direction for RTOG bladder cancer preservation to include patients who are non-cystectomy candidates.
Salvage radiation therapy after radical proctectomy. The GU Committee was planning to evaluate the role of COX2 inhibitors in this setting. Recent COX2 toxicity data has slowed progress to developing a successor trial to RTOG 9601 but efforts are continuing to develop a viable concept.
Hypofractionation. CTEP has rejected the RTOG proposed Phase II study in hypofractionation for low risk prostate cancer. Nevertheless, there continues to be strong interest in the group and a meeting will be held with CTEP to discuss issues and perhaps resubmit this concept.
AMG-126. Dr. Roach is continuing to work on the Amgen compound for patients with metastatic prostate cancer. This trial will not have a survival endpoint and is being directed thru Cancer Control.
A companion trial to RTOG 0232 will obtain fresh tissue at the time of prostate brachytherapy and will allow us to study significant gene related radiotherapy questions. A pilot/feasibility trial is high priority for the Genitourinary Cancer Committee.
4. OTHER ISSUES
Dr. Gomella updated the group on urology issues and Dr. Pollack updated the group on the substantial progress of the TRP Section of the Genitourinary Cancer Committee.
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Howard Sandler, M.D., Chair
1. ACTIVE TRIALS
A. RTOG 9902 - Will be amended to improve patient accrual.
B. RTOG 0126 - Since the IMRT amendment was approved, most US centers are treating with IMRT. Accrual has been very good for this trial.
C. RTOG 0014 - Dr. Pienta has made some adjustments to the eligibility criteria in an effort to assist with accrual, as his trial has not been accruing at its expected rate.
D. RTOG 0233 - This trial continues to accrue well at the accrual rate of previous RTOG bladder cancer trials.
E. RTOG 0215 - Continues to enroll patients from RTOG 9910 for an evaluation of the efficacy of Viagra and patients with sexual disfunction.
F. RTOG 0232 - A Phase III brachytherapy study has begun to accrue.
G. RTOG 0321- An activated HDR brachytherapy trial. Once institutions are accredited, it is expected accrual will be brisk.
2. PENDING STUDIES
A. RTOG 0336 - Is a developing concept for Herceptin and Taxol and radiation therapy for bladder preservation in non-cystectomy, invasive, bladder cancer cases. This concept continues to move forward.
B. We are continuing to move forward for a prostate cancer, post-prostatectomy, salvage radiation therapy trial following biochemical failure. Dr. Pollack is working to develop a COX2 inhibitor trial.
C. Dr. Chakravarti discussed our plan to obtain in a pilot manner tissue from RTOG 0232 that could be used to obtain DNA microarrays for subsequent analysis.
3. Dr. Chakravarti presented a translational research talk.
4. The Genitourinary Cancer Committee heard updates from Urology and Translational Research from Dr. Gomella and Dr. Pollack.
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Howard Sandler, M.D., Chair
I. Active Trials:
RTOG 9902: Accrues at a rate of approximately eight patients per month. A total of approximately 350 patients have been accrued. Dr. Rosenthal stated there will be a design to help approve accrual presented several amendments.
RTOG 9910: This trial continues to accrue well. It will close in 2004 and no comments or adjustments are planned.
RTOG 0011: This trial has accrued a total of 51 patients. Accrual is slow, for reasons that remain unclear. It is likely that relatively few patients are referred to Radiation Oncology by Urology for adjuvant treatment. This trial will be reviewed by the RTOG Data Monitoring Committee in February 2004.
RTOG 0126: This phase III trial is accruing well. Importantly, an IMRT amendment was recently approved. It is likely that this amendment will further escalate the accrual rate, in addition to the closure of RTOG 9910 in 2004, which competes.
RTOG 0014: This trial evaluates the role of chemotherapy as early treatment for patients with a rapidly rising PSA following the failure of localized treatment. The trial is active in SWOG, CALGB, and ECOG. One SWOG patient has been accrued through the CTSU mechanism. This trial will be featured at a special clinical trial session at the 2004 ASCO meeting. Additionally, pocket-sized cards outlining the protocol eligibility requirements were made available to the RTOG committee members.
RTOG 0233: This randomized phase II bladder cancer trial is accruing at the usual rate for RTOG bladder preservation trials. Many patients are being accrued from Massachusetts General Hospital. Hopefully, wider institutional accrual will occur.
RTOG 0215: This trial continues to examine the role of Viagra for sexual dysfunction that occurs in patients treated in RTOG 9910.
RTOG 0232: This phase III brachytherapy trial is open and accruing. Many institutions are going through the credentialing process.
Dr. Cohen and Dr. Warde presented updates of the American Cooperative Group Localized Prostate Cancer Trials and the EORTC and Canadian Localized Prostate Cancer Trials, respectively. This 15-minute presentation was well received by the committee membership.
II. Pending Studies:
RTOG 0321: This study will be activated shortly. This is the HDR Prostate Brachytherapy trial. Dr. Hsu presented a brief synopsis.
Dr. Allen Pollack updated the group on both the TRP activities, including a planned fresh tissue prostate cancer trial piggybacking onto RTOG 0232, and a discussion of the role of rising PSA after surgery. The group continues to work to refine a rising PSA prostate cancer trial.
Robert Lee presented the rationale for phase III hypofractionation trial. This novel therapy will have high priority within the group.
Dr. Janaki Moni presented a cancer control study involving the role of Saw Palmetto in relieving the acute urinary effects associated with radiation therapy.
Dr. Roach presented a proposal for an AMG-162 trial in patients with metastatic prostate cancer.
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Howard Sandler, M.D., Chair
1. ACTIVE TRIALS
- RTOG 9902 - Continues to accrue slowly with approximately 5 to 10 patients per month. The overall accrual rate will be assessed by the Data and Safety Monitoring Committee in January 2004.
Dr. Rosenthal will develop several amendments to assist with accrual.
- RTOG 9910 - Continues to accrue very well. No modifications are planned. This trial will close in 2004 and intermediate risk patients who are eligible for RTOG 9910 will be eligible for RTOG 0126.
- RTOG 0011 - Is currently active in its two-arm form. Accrual remains modest and Dr Valicenti will continue to contact people frequently to encourage additional accrual.
- RTOG 0014 - Evaluates the role of chemotherapy as early treatment for patients with a rapidly rising PSA following local treatment. The trial is active and has the support of SWOG, CALGB, and ECOG.
- RTOG 0126 - Is a phase III dose escalation study. Dr Michalski will develop an IMRT amendment as soon as possible and it is expected that this amendment will be approved prior to the next group meeting.
- RTOG 0215 - Continues to enroll patients from RTOG 9910 for assessment for use of Viagra.
- RTOG 0232 - Is a phase III brachytherapy study. Dr. Prestidge is the PI. The trial is active and represents an important phase III study for RTOG that will examine outcome measures including cancer outcome, quality of life, and cost.
- RTOG 0233 - Is a randomized phase II bladder cancer trial. This trial is active and is accruing as is typical for previous RTOG bladder cancer trials.
2. PENDING STUDIES
- RTOG 0321 is a proposed phase 1/2 high dose brachytherapy trial Joe Hsu is continuing to work with RTOG Headquarters for protocol activation. This trial remains our number 1 priority for activation.
- Spirit Trial. This trial has been accruing slowly in ACOSOG and for now the RTOG will not participate directly since it will use valuable headquarter resources and institutions can enroll patients can enroll patients thru ACOSOG.
- RTOG 0336 is a phase I/II radiation therapy surgery paclitaxel and trastuzumab concept for patients who are not eligible for radical cystectomy and have bladder cancer. This trial opens a new front in the GU Committees bladder cancer strategy and, based on previous discussions within the group, represents a patient population that could potentially benefit from prospective clinical trials.
- RTOG 0337 is a proposed randomized study of COX2 inhibitor Celebrex for rising PSA following radical prostatectomy. Alan Pollack is continuing to work with industrial sponsors to develop this concept further.
3. The GU Committee heard updates regarding Urology and Translational Research from Dr
Gomella and Dr Pollack respectively.
4. Closed studies were briefly reviewed.
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Howard Sandler, M.D., Chair
RTOG 9601 - Dr. William Shipley was not present to talk to us about this study. This study has accrued well and is now closed.
RTOG 9902 - This study was temporarily closed, reopened, and is now accruing at a rate of 10 patients per month.
RTOG 9910 - This study is accruing very well. There was a transient decrease in accrual. It is unclear what the reasons for this are, but overall the accrual rate is excellent.
RTOG 0011 - This study evaluates adjuvant post-prostatectomy therapy has been accruing slowly. It is being revised to include 2 arms, both of which have radiation therapy, and it is expected that this will result in improvement in accrual.
RTOG 0126 - This study was reviewed by Dr. Jeff Michalski. The study is accruing well and Dr. Michalski is in the process of developing IMRT guidelines.
RTOG 0014 - This study which evaluates the role of chemotherapy as early treatment for patients with a rapidly rising PSA following local treatment failure is open.
RTOG 0233 - This study is a randomized Phase II bladder cancer trial has recently been activated.
RTOG 0215 - This study is a Viagra companion study to RTOG 9910 and has been recently activated.
RTOG 0052 - This study is a proposed NCCTG trial evaluating the use of total Androgen Suppression and Brachytherapy for locally recurrent prostate cancer after external beam treatment was re-discussed. Accrual has been slow in the NCCTG and whether RTOG will participate in this study will be re-evaluated at the next meeting.
RTOG 0232 - A Phase III Brachytherapy study is moving thru the activation phases and should be definitely be activated before the summer meeting.
Joe Hsu presented his latest version of the HDR brachytherapy study. This study is high priority for headquarters to activate.
SYSTEMIC RADIOTHERAPY
Dr. Rajan presented again the concept of Systemic RT and Chemotherapy. The current study included Strontium and Docetaxel in hormone refractory prostate cancer. Hopefully this study will develop enough momentum to be activated soon.
SPIRIT
Lou Potters talked about the Spirit Trial. This study has been accruing slowly thru ACOSOG. If the accrual rate picks up and the study has a good chance of success, RTOG will endorse it enthusiastically at the next meeting.
TRP
Dr. Pollack updated the group on the active translational research program, especially the planned study of markers and the RTOG 9202 prostate cancer tissue bank. The role of hypo fractionation was discussed briefly.
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Howard Sandler, M.D., Chair
RTOG 96-01
This study was updated by Dr. William Shipley. The study is accruing well and is expected to close in Spring 2003. There were recent amendments to allow for treatment around hip arthroplasties. It will still be required to have pathologically negative lymph nodes at the time of radical prostatectomy to be enrolled.
RTOG 99-02
This study was reviewed by Dr. Rosenthal. This study temporarily closed since the last RTOG meeting due to an increased incidence of thromboembolic events. The study was revised and reapproved by CTEP. This study has since been reactivated and members were encouraged to submit the revised protocol to their IRBs for additional patient accrual.
RTOG 99-06
This study was review by Dr. Kaufman. This bladder cancer study accrued steadily and completed its planned accrual. A total of 22 institutions participated. Dr. Kaufman also indicated that RTOG would participate in an international EORTC designed metastatic bladder cancer study evaluating the role of two different chemotherapy regiments. This study was developed with the Genitourinary Global Group and will potentially allow for further productive collaborations with this group in the future.
RTOG 99-10
This study was reviewed by Dr. Tom Pisansky. It is accruing well and will complete accrual in September 2003. Accrual has accelerated recently and may approach more than 50 patients per month on a regular basis. The successor study to this will be P-0126 and institutions not credentialed for that study were encouraged to do that as soon as possible. Dr. Pisansky also presented N-0052, total androgen suppression brachytherapy for locally recurrent prostate cancer after external beam treatment. Dr. Kuban was named to be the RTOG lead person on this. This study will be discussed at Research Strategy for approval.
RTOG P-0011
This study was presented by Dr. Richard Valicenti. This study has been open for nearly a year and does not have an active accrual at present. There was some discussion regarding potential barriers to accrual including the potential toxicity of the GnRH agonists. It was also noted, optimistically, that NCIC has approved this study and hopefully will begin accrual shortly. Members will be encouraged to discuss this study with their urologist and to indicate that this study is explicitly for high risk patients, i.e. those that have a very high risk of biochemical failure following prostatectomy.
RTOG P-0126
This study was presented by Dr. Jeff Michalski. This recently opened phase III dose escalation study will not include IMRT at present but will at some future point.
JPR.7 NCIC
Continuous verses intermittent androgen ablation after radiation therapy. Dr. Juanita Crook presented a brief update of this study. This study is accruing well with 550 patients that have been entered and the total accrual goal is 1,340. The baseline PSA for study entry has been reduced from 6 to 3.
CARAFATE
A previously discussed carafate study will not be pursued further within the group. There has not been available support for generating a placebo control design.
RTOG P-0014
Chemotherapy for failure of local therapy. Dr. Pienta indicated that this study will be activated shortly. Chemotherapy regiments have been modified slightly based on the toxicities observed on RTOG 99-02.
HDR
Joe Hsu updated the group on the status of the HDR trial. Both Dr. Hsu and RTOG headquarters have been actively finalizing this trial. Patients will be able to receive HDR either before or after external beam therapy. However each institution will select one or the other of these sequences and stick with that to avoid potential bias.
SYSTEMIC RADIOTHERAPY
The Systemic Radiotherapy and Chemotherapy trial proposal was updated by Dr. Rajan. The group has agreed to name Dr. Rajan as the RTOG CTSU person on the MD Anderson Cancer Center phase III study and at the same time continue to pursue the Strontium and Taxol phase II concept.
BLADDER CANCER
Dr. Zeitman reviewed the new phase II bladder cancer study that should be activated soon. This randomized phase II builds on previous bladder cancer experience within the group. There was a discussion regarding whether the platinum given on day one could be perhaps given between the two BID radiation fractions to make the study timing more manageable.
SPIRIT
Juanita Crook presented an update of the SPIRIT trial. This carefully designed study is being run through ACASOG and compares brachytherapy and radical prostatectomy for early prostate cancer patients. This randomization is expected to be difficult and a considerable per case reimbursement is a part of this trial. There is some enthusiasm among the committee members for this trial and it will be discussed more thoroughly at research strategy.
UROLOGY
Dr. Gomella updated the group on urology issues including the naming of an urologist, Dr. Andrew Von Eschenbach, as the new director of the NCI.
TRP
Dr. Alan Pollack updated the group on TRP activities. Several secondary analyses of markers in RTOG 86-10 patients and RTOG 92-02 patients are underway. Dr. Pollack also presented a concept for patients who are not cystectomy candidates and have muscle and bladder cancer. Those patients may receive C225 and weekly Paclitaxel. This concept will be brought forward to research strategy.
OTHER ISSUES
It was noted that RTOG 90-19/ SWOG 8794 is expected to be reported in 2004.
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Howard Sandler, M.D., Chair
1. CURRENT STUDIES
A. RTOG 96-01. This study is accruing at approximately 20 patients per month. It has reached approximately half of its accrual goal. Minimal liver toxicity has been reported.
B. RTOG 99-02. This study is accruing at about 10 per month. The Committee was encouraged to continue to have discussions with Urology and Medical Oncology to facilitate accrual. Headquarters is working on drug delivery issues. Further discussions will be required to facilitate this. Recommendation was made to consider elevating the upper limit of PSA for eligibility. Currently this is 100.
C. RTOG 99-06. This cancer-bladder preservation trial is accruing at approximately 2-3 patients per month. Acceptable toxicity is reported.
D. RTOG 99-10. Minor amendments were discussed. This study is accruing faster than projected at over 30 patients per month. The Committee was congratulated on its excellent work in accruing patients for this trial.
E. P-0019. This prostate brachytherapy trial is accruing well. Recently close to 10 patients per month have been entered. No issues were raised.
2. PENDING STUDIES
A. RTOG P-0011. An adjuvant radiation and hormone therapy trial will be activated this summer after a long gestation period. This large study has the support of ACOSOG. Dr. Valicenti will initiate discussions with EORTC for possible support as well.
B. RTOG P-0014. This chemotherapy-for-failure-of-local-therapy study has been approved by the CTEP and will be activated as soon as possible.
C. RTOG P-0126. Phase III Dose Study was discussed briefly and is also approved by the CTEP and hopefully will be activated in the near future. Institutions will need to be credentialed before accruing patients. Approximately 1500 patients will be required for this study.
D. NCCTG N0052, RTOG 1025. This brachytherapy and hormone therapy study for external beam failures was briefly discussed and the Committee was updated to its status. This protocol is at CTEP.
3. OTHER ISSUES
A. Dr. Sandler updated the Committee on the preliminary review of the GU Section of the RTOG Grant. A tentative recommendation for additional 6-years of funding was made.
B. Urology update. Dr. Gomella updated us on the ACOSOG radical prostatectomy versus brachytherapy trial for early prostate cancer. This study will have a companion quality of life trial as well. A total of approximately 1500 patients will be enrolled to detect an overall survival difference of 20%.
C. Bladder Cancer. The Committee discussed a proposed randomized Phase II Study, which will compare induction chemotherapy with Taxol Cisplatin and bid radiation therapy versus 5 FU and Cisplatin plus bid radiation. Adjuvant chemotherapy with gemcitabine and paclitaxel will be used. There was enthusiastic support for this trial by the entire Committee.
D. The EORTC Randomized Study looking at 2 different, non-MVAC regimens were discussed. Dr. Kaufman presented the background for this study, and again, there is support for this non-radiotherapy study.
E. Translational research. Dr. Pollack updated the group on the current status of RTOG 86-10 Marker studies and planned RTOG 92-02 Marker Studies. Investigators who have an interest in Markers were informed that there is adequate tissue from RTOG 86-10 and proposals could be entertained at the GU/TRP Meeting.
F. The Phase III Brachytherapy Trial was presented by Dr. Sanda. This trial has the support of the Committee. This is primarily designed for patients who have already shown a preference for brachytherapy as their primary treatment. There was a discussion about broadening eligibility to include more early patients. This will be discussed with biostats to determine how this would affect the study design. In addition, the Committee feels strongly that a PSA endpoint should be the primary study endpoint.
G. HDR Brachytherapy. This concept was presented by Jay Hsu. Again, the Committee is supportive of a clinical trial investigating HDR Brachytherapy with primary endpoint, at this stage of assessing toxicity.
H. Systemic radiotherapy was strontium and chemotherapy, using docetaxel, was reported by Dr. Rajan. Based on recent M. D. Anderson data, there is strong support for this trial.
I. Mike Gillin briefly updated the group on the current status of the closed prostate brachytherapy trial RTOG 98-05. An Abstract has been accepted for presentation at AAPM.
J. HRQOL. Rich Valicenti presented an outcomes trial using NESP to decrease symptomatic anemia in men treated with external beam radiation therapy and androgen ablation. There was enthusiastic support for this concept as well.
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Howard Sandler, M.D., Chair
OPEN STUDIES:
RTOG 94-06 - Dr. Michalski reviewed the current status of RTOG 94-06. The study is accruing at the fifth dose level and is expected to close in the next four to six months. It was agreed to further pursue with the design of a phase III study using the maximum tolerated dose of RTOG 94-06 as the high dose arm and 70 Gy as the low dose arm. No androgen ablation will be allowed in this study and the concept for the randomized study should be submitted to CTEP.
RTOG 94-08 This study will reach its accrual goal this year. Dr. McGowen presented data indicated that monthly accrual is still active. Final statistical analysis finally will be eight years after the completion of the trial. Interim analysis will be performed in approximately two years.
RTOG 96-01 Dr. Shipley indicated that this study has reached double-digit monthly accrual recently. The protocol has been modified to allow additional PSA assays. In addition, the lower eligible limit of PSA is now 0.2. In addition, Dr. Shipley will amend this study to allow CT of the pelvis alone rather than CT of abdomen and pelvis as a pre-study entry test. Toxicity from the double-blinded drug has been acceptable.
RTOG 99-02 Dr. Seth Rosenthal presented accrual data for this chemotherapy study. Twenty patients have been entered to date. Discussion continues with pharmaceuticals companies to assist with drug supply. These discussions are occurring both in Canada and in the US.
RTOG 99-06 Dr. Kaufman presented the current status of this chemotherapy study. Most accrual, which has been approximately two patients per month, which was expected, has been from one institution. The general committee membership was strongly encouraged to open this study and participate.
RTOG 99-10 Dr. Tom Pisansky indicated that this study although only opened recently has been accruing well. He indicated that there are discussions with manufacturers regarding hormone therapy supply.
DEVELOPING STUDIES:
RTOG 1028 Dr. Pienta has submitted a study for chemotherapy following local failure after prostate cancer. This study has been submitted to CTEP. Comments were received and the revised concept is ready for resubmission.
RTOG 1037 Rich Valicenti presented the current status of developing study 1037. This three-arm study will compare adjuvant radiation therapy alone, adjuvant radiation therapy two years of androgen ablation, versus two years of androgen ablation alone for high-risk prostate cancer for patients following radical prostectomy. This study will need to accrue approximately twenty seven hundred patients. It has been approved by the concept evaluation panel. Details of androgen ablation remain to be worked out and it was recommended that Dr. Valicenti keep the accrual as broad as possible to facilitate accrual. The NCIC has agreed to participate in an intergroup manner.
RTOG 1064 Robert Lee presented the current status of phase II brachytherapy study consisting of external beam and brachytherapy. The study has been submitted to the NCI. There was discussion to broaden the study to include palladium as well as iodine. Sentiment was strongly in favor of broadening the study in this way, as long as it does not substantially affect total accrual.
Bladder cancer issues were discussed by Drs. Shipley and Kaufmann. There has been a proposal to participate in an EORTC phase III study for metastatic bladder cancer. This will allow RTOG to participate in international bladder cancer trials and will facilitate any future planned RTOG led phase III studies. The committee supported the concept for this chemotherapy only study and it will be presented to Research Strategy.
The committee heard a presentation from representatives from the CTSU. It was noted that two RTOG studies are in the CTSU menu including RTOG 96-01 and RTOG 99-10.
Translational Research
Alan Pollack reviewed the current status of translational research studies in RTOG 86-10 and plans for RTOG 92-02. It is expected that additional analysis will be useful in grant development and future RTOG studies.
Phase III Brachytherapy Study
Bradley Prestidge presented a concept for a phase III study involving brachytherapy. The concept suggests half of the patients would receive brachytherapy alone and the other half would receive external beam followed by brachytherapy. Patients would be eligible if they have general favorable disease, but one adverse prognostic factor. Based on comments from the steering committee and from the general GU committee Dr. Prestidge will revise his concept and recirculate it. It is expected that this study would become active once the current phase II study is complete and analyzed.
Dr. Sandler suggested to the group that the Canadian institutions would be able to use Buserelin (Suprefact) for RTOG studies 99-02 and 99-10. This drug is available in Canada but not in the United States. Once pharmalogic data is reviewed and determined to be equivalent to agents available in the American market, protocols RTOG 99-10 and RTOG 99-02 will be amended.
The concept was reviewed for systemic radioisotope therapy with strontium and chemotherapy. Dr. Raghu from Montreal presented the concept. A brief discussion followed and although there is scientific rationale for this study, it was felt important to assess the level of enthusiasm within the group for pursuing this concept. A similar concept had been introduced to the group several years ago but was reportedly not enthusiastically supported by the NCI during the last site visit.
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