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Lisa Kachnic, M.D., Chair
PROTOCOLS
RTOG 0433 - This phase III of re-irradiation for bone metastases study was activated in March 2005 and has accrued 41 of the required 650 patients.
RTOG 0435 - This phase III of palifermin versus placebo for mucositis has approximately 5 sites accruing out of potential 70 who have IRB approval. An amendment to open the study to post-operative patients was discussed. Amgen data is needed about post operative palifermin prior to initiating the amendment. Subsequent to the RTOG semi-annual meeting, this study was closed based on data completed Amgen studies.
RTOG 0517 - This phase III study of zoledronic acid +/- isotopes for palliation of bone metastases was activated in July 2006 and has accrued 43 of the required 352 patients.
RTOG 0518 - This phase III study of zoledronic acid versus placebo to prevent osteoporosis was activated in March 2006 and has accrued 53 of the required 1272 patients. An amendment to drop the placebo was discussed, and hardcopy changes to the protocol were received from the Study Chair.
RTOG 0537 - This phase II/III study of ALTENS versus pilocarpine was reviewed by the DCP and they requested revisions. The protocol is due to be resubmitted on February 15 subsequent to the RTOG meeting and an extension for resubmission until February 29 was approved.
RTOG 0614 - This phase III study of memantine for cognition is a joint study by the Brain/Symptom Management Committees. There was a discussion about the need for submission to the FDA and for IND. Subsequent to the meeting: The study is IND exempt and does not need to be submitted to the FDA. It is scheduled to be activated in February.
RTOG 0631 - This phase II study of stereotactic radiosurgery is a joint study by the Brain Tumor and Symptom Management Committees. DCP approved the concept and RTOG Headquarters has the draft protocol. The protocol needs for the Medical Physics section to be added.
RTOG 0818 - This phase II study of brachytherapy fractionation for vaginal length is a DCP concept is in progress. There was a discussion of needing funding for the device involved and training sites to use it.
RTOG 0831 - This phase III study of tadaafil versus placebo for erectile dysfunction is in the process of becoming an RTOG study, as the funding for the Fox Chase Cancer Center CCOP was not renewed. The Study Chair is working on a draft of the protocol. Fred Osmers needs to contact Lilly Oncology and confirm support.
RTOG DEVELOPING - This developing protocol for patients to be screened for depression after receiving radiation therapy or in follow-up post radiation therapy. Overall the committee and DCP are interested, as there is little data on depression. Consent may be a problem. Is there any pilot data? Could this be funded under the survivorship office?
RTOG DEVELOPING - This developing protocol for low intermediate risk prostate patients is a comparison of patient report outcomes (PROs). Is this an equivalency study with an emphasis on cost effectiveness? The Study Chair should apply for an R01 for this undertaking.
RTOG DEVELOPING - This developing protocol about available assessment tools. They are Cella's PROMIS and the BFI. "Fatique" should be defined. Pilot studies to do this will be performed through active RTOG prostate studies before considering a phase III effort. Patients must be given Web access for the PROMIS; funding may be available through NCI for "correlative" studies.
RTOG DEVELOPING - This developing protocol for vitamins for side effects of treatment. Not enough site specific information available about this study and cannot move forward at this time.
RTOG DEVELOPING - This developing protocol for cancer prevention in head and neck patients. There are two potential concepts one is looking at modulation of biomarkers in successfully treated patient. A pilot study can be done to show feasibility. The second is curcumin in prevention of skin toxicity; there is animal data showing statistically significant increases in the healing rate and decreases in inflammation.
OTHER BUSINESS
The Symptom Management Committee is now an umbrella under the Outcomes and Health Services Research Committee similarly to the Quality of Life Committee. Dr. Larry Berk is the Vice Chair for CCOP Research Base and Dr. Lisa Kachnic is the Chair of the Symptom Management Committee. The Chair of the Translational Research Program is willing to work with the committee regarding collection of samples to identify markers to predict symptoms, e.g., markers of decreased cognition or increased side effects.
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Lisa Kachnic, M.D., Chair
Protocols
RTOG 0123 - The study was activated in June 2003 and has accrued 78 of the required 205 patients. Closure of this study for poor accrual is scheduled for August 3, 2007.
RTOG 0433 - The study was activated in March 2005 and has accrued 26 of the required 650 patients. The trial is doing well.
RTOG 0435 - The study was activated in July 2006 and has accrued 9 of the required 290 patients. An amendment including: (1) use of a revised mucositis module, (2) the addition of a xerostomia patient questionnaire, (3) removal of the CTC toxicity scale, and (4) an increase in funding per patient to $4500 CCOP and $5500 non-CCOP was submitted to DCP on May 23.
RTOG 0517 - The study was activated in July 2006 and has accrued 24 of the required 352 patients. There was a discussion regarding the need for medical oncology awareness in attempts to boost accrual. An additional $1500 of funding is available per patient.
RTOG 0518 - The study was activated in March 2006 and has accrued 37 of the required 1272 patients. A concern was raised regarding the placebo arm as many medical oncologists use bisphosphonates despite the paucity of supporting data. Also, an additional $1000 of funding per patient is available to support dexa scans.
RTOG 0537 - DCP has approved the concept; however, PIs in the U.S. cannot receive reimbursement from insurers for ALTENS. The Study Chair is applying for grant funding from NIH Alternative Medicine agencies to fund reimbursement. Until this funding is approved, this study will not be developed further.
RTOG 0614 - This is a joint study by the Brain/Symptom Management Committees. The final draft of this developing protocol is in process.
RTOG 0616 - The protocol is being reviewed by DCP.
RTOG 0631 - This study is a joint study by the Brain/Symptom Management Committees. The study concept was submitted to DCP May 17. The concept was reviewed by DCP June 13 and is now with the lead reviewer.
RTOG 0632 - The study concept was submitted to DCP April 4. The concept was reviewed by DCP May 30.
RTOG 0725 - There was discussion regarding changing the primary endpoint from vaginal length to patient perceived sexual function via SAQ. Dr. Bruner wishes to maintain vaginal length as the primary endpoint. This developing concept was approved by the RTOG Research Strategy Committee.
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Lawrence B. Berk, M.D., Ph.D., Chair
Active Studies
RTOG 0123 - A Phase II study using Captopril for small or non-small cell lung cancer. The study/site chairs will evaluate the eligibility and enrollment criteria for a final time to determine if there are any actions that can be expected to significantly improve enrollment. If not, this study will be closed.
RTOG 0127 - A Phase III study with ECOG (5597) for non-small cell lung cancer using Selenium. RTOG has accrued 63 patients.
RTOG 0215 - A Phase III study using Sildenafil for treatment of Erectile Dysfunction. This study will be closed subsequent to the June RTOG meeting due to poor accrual.
RTOG 0315 - A Phase III study for radiation therapy induced diarrhea using Sandostatin versus placebo. The study has accrued 221 of the required 226 patients.
RTOG 0433 - A Phase III study with NCIC (CTG SC.20) of re-irradiation for single versus multiple radiation therapy fractions and bone metastases. RTOG has accrued 5 patients.
Developing Studies
RTOG 0431 - A Phase III prostate study using LHRH +/- AMG-162 for bone metastases. This is now a treatment study and will be submitted to CTEP by the Headquarters GU Team.
RTOG 0435 - A Phase III head and neck study using KGF versus placebo during radiation and chemotherapy for mucositis prevention. This study is close to being approved by DCP. Projected activation is February or March, 2006.
RTOG 0517 - A Phase III breast and lung study using bisphotphonates +/- radioisotopes for bone metastases. DCP has approved the concept in November, 2005. The full protocol will be submitted in February, 2006.
RTOG 0518 - A Phase III prostate study using RT/LHRH/placebo versus RT/LHRH/bisphosphonate for prevention of osteoporosis. The DCP review was received January 13th with minor changes requested. The protocol is due to DCP on February 10, 2006.
RTOG 0528 - A Phase III breast study using Calendula versus placebo for prevention of RT dermatitis. Boiron, the industry sponsor, may support the study. Raygel® may be substituted if Boiron does not provide support.
RTOG 0530 - A Phase II head and neck chemoprevention study using Omega-3 fatty acids. Since statins were found to be ineffective in prevention of head & neck cancer, Omega 3 fatty acids were discussed as an alternative. Industry support will be sought.
RTOG 0532 - A Phase III prostate study using Balasalazide versus placebo for prevention of pelvic RT entertis. Potential replacement for RTOG 0315 Sandostatin®. Will request the industry sponsor be willing to expand the study population beyond prostate patients.
RTOG 0535 - A Phase II lung, prostate and breast study using Ginseng versus placebo. Dr. Berk wants to be sure the industry sponsor will support a follow up phase III study prior to developing this study.
RTOG 0537 - A Phase II radiation therapy induced xerostomia study using pilocarpine versus eletroacustim. Study chair is drafting this concept.
RTOG 0614 - A Phase III brain study using WBRT +/- Namenda to prevent cognitive dysfunction. The Headquarters Brain team will submit this concept to DCP. WBRT dose will be modified to 37.5 Gy.
RTOG 0616 - A Phase III prostate study using Sildenafil for erectile dysfunction. Fox Chase Cancer Center will submit study to DCP. RTOG will add logistics to the DCP approved protocol similar to RTOG 0433.
RTOG 0620 - A spinal compression study using standard radiation therapy versus high dose radiation therapy with SBRT/IMRT. Approved by the CCOP Research Strategy Committee but not fully approved by the RTOG Research Strategy Committee. Some of the issues which were raised are a lack of resources for this population, some sites do not use IMRT for this population, and concerns with IMRT turn around. The study chair may revise the concept for presentation in June 2006 to Research Strategy.
Developing Concepts
RTOG XXXX - A Phase II breast study using Raygel® versus placebo for prevention of skin toxicity. Already approved by the CCOP Research Strategy Committee but not yet presented to the RTOG Research Strategy as it competes with RTOG 0528. Raygel® may be substituted for calendula (see RTOG 0528 above).
RTOG XXXX - A Phase III pelvic study using Vitamin A for post-pelvic radiation therapy. This study would have to be limited to non-smokers. Dr. Berk will investigate funding for distribution of vitamin A through CAM. The concept has been circulated to the appropriate Headquarters team in July 2005, which needs statistical feedback.
RTOG XXXX - A Phase III head and neck study using Acidophilus for radiation therapy induced thrush. This concept competes with the mucositis trials, and most physicians will give Diflucan® for thrush. In addition, industry support for the study will need to be identified.
RTOG XXXX - A Phase II head and neck post treatment study using raspberry extract to prevent new primaries. This concept has not yet been received at RTOG Headquarters.
Other Business
Dr. Berk requested RTOG 0435 and all CCOP concepts involving TRP can be circulated to Dr. Dicker, the new Translational Research Program Chair, for review and feedback.
Dr. Scarantino discussed the possibility of study radio protectors in a future survivorship/late effects trial.
Dr. Berk discussed a new agent for prevention of hair loss during WBRT, but NCI would need to contract with an industry sponsor for supply and distribution of the agent.
Dr. Turner raised the issue of addressing the symptoms that are most difficult for patients. Dr. Bruner suggested soliciting studies from researchers that would address the primary symptoms that patients identify.
CCOP Priorities: RTOG 0435, 0518, 0517 & 0537.
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Lawrence Berk, M.D., Ph.D., Chair
ACTIVE STUDIES
RTOG 0123 - As of 6/20/05, the study has accrued 32 of the required 205 patients. Per the Symptom Management Committee, this study must be consistently accruing 4 patients per month by the next RTOG meeting, or it will be closed. Drs. Berk and Kachnic will request Dr. Choy promote this study to the Lung Cancer Committee members to aid accrual.
RTOG 0127 - ECOG 5597: As of 6/20/05 RTOG has accrued 55 cases.
RTOG 0215 - Amendment 2, opening this study to patients similar to the cohort on RTOG 9911, was broadcast on 6/1/05. This amendment may increase accrual to the study.
RTOG 0315 - As of 6/20/05, the study had accrued 143 of the required 226.
RTOG 0433 - NCIC CTG SC.20: DCP reviewed this study on 6/17/05. NCIC to respond to the review by 7/11/05. RTOG will re-open the study to accrual when DCP has approved the study.
DEVELOPING STUDIES
RTOG 0419 - RTOG HQ has Kachnic's DCP concept; needs statistics. Industry sponsor, OSI, may withdraw support if this concept isn't moved forward in very near future.
RTOG 0431 - Drs. Roach and DeSilvio discussing endpoints. There will be a conference call to finalize endpoints and assessments.
RTOG 0435 - Protocol to be submitted to DCP the 2nd week of July.
RTOG 0517 - DCP has just reviewed this concept; review to be sent to RTOG HQ. Seider requests conference call with study chairs and HQ to respond to DCP's review. There will be a conference call to finalize endpoints and assessments.
RTOG 0518 - DCP approved concept; protocol in development. There will be a conference call to finalize endpoints and assessments.
RTOG 0528 - With statistics.
RTOG 0530 - Funding needs to be found for the statin.
RTOG 0531 - RTOG HQ has DCP concept and draft protocol.
RTOG 0532 -This potential replacement for 0315 (Sandostatin®) will be discussed further by the Committee; the endpoint may be unrealistic for the rectal cancer population.
RTOG 0535 - Canadian manufacturer will supply and distribute the two forms of ginseng in this study. The revised, 3 arm trial will be submitted to DCP as a full protocol. Application will be made for supplemental CAM funding from the NCI.
CONCEPTS
A phase II breast study using Raygel ® vs. placebo for prevention of skin toxicity. The concept has been approved by the CCOP Research Strategy Committee for development.
This study would have to be limited to non-smokers. Funding for distribution of vitamin A would have to be identified. RTOG HQ has not received a concept for this study. The study will be discussed in an upcoming CCOP Research Strategy conference call.
A phase II lung study using inhaled steroids. This concept is not a high priority for development at this time.
A phase II radiation therapy dose-seeking study. Approved by the CCOP Research Strategy Committee, but RTOG Research Strategy Committee has strong reservations and recommend further discussion by and feedback from the RTOG Brain Committee prior to development. Berk and Regine will contact Mehta.
A head and neck study using acidophilus for RT-induced thrush. This concept competes with the mucositis trials, and most physicians will give Diflucan® for thrush.
A phase II study for head and neck chemoprevention patients using raspberries for prevention of second primaries. This concept was not discussed by the Committee at this meeting. Funding for the raspberries would be needed.
A phase II head and neck study using electroacustimulation and pilocarpine for xerostomia. Approved by the CCOP Research Strategy Committee for development but not yet presented to RTOG Research Strategy. This will be a limited institution study.
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Lawrence B. Berk, M.D., Ph.D., Chair
I. Introduction:
Dr. Lawrence Berk discussed the RTOG/CCOP grant renewal application process with the upcoming due date of July 14th, 2004. He thanked Deb Bruner, Chuck Scarantino, Sophie Turner and especially Lisa Kachnic for assistance in the preparation of the renewal application. He summarized the successes of the last 5 years of CCOP funding including the completion of RTOG 9714. He noted the analysis of several completed RTOG studies identified a disconnection between physician reported and patient reported outcomes (as in the RTOG trials of Pilocarpine and Amifostine). He stressed the importance of the collaborative efforts of the Symptom Management and Outcomes Committees to develop more sensitive outcome reporting mechanisms, as well as to formulate statistical strategies to power patient-reported endpoints for future site-specific treatment trials.
II. Symptom Management:
Dr. Lisa Kachnic reported on the Symptom Management Committee efforts, emphasizing the request for new concepts to be initially presented to Drs. Kachnic and Berk in advance of future meetings. The closed protocol analysis and open protocol update was then summarized by Dr. Kachnic.
III. Closed Trials Update:
RTOG 9714 - Bone Metastases: Similar pain relief and health-related QL improvements on both arms. Two ASTRO 2003 abstracts (outcomes-Hartsell and QOL-Bruner) and an upcoming JNCI publication on outcomes (Hartsell). Dr. Bruner preparing QOL manuscript.
RTOG 9801 - Amifostine for Lung: Disconnect between similar physician-reported outcomes between the two arms and improved patient-reported swallowing with Amifostine. ASCO 2003 abstract (Movsas) and ASTRO 2003 abstract (Werner-Wasik). Outcomes manuscript completed (Movsas) and to be sent for RTOG review.
RTOG 9809 - Negative trial; final draft of outcomes manuscript under review (Pilepich).
RTOG 9901 - Negative trial; initial draft of outcomes manuscript written (Laveque).
RTOG 9913 - Biafine for H&N: Negative trial; initial draft of outcomes manuscript in progress (Elliott).
RTOG 0119 - Melatonin for Brain Mets: Preliminary analysis reveals similar survival and minimental outcomes. Accepted for 2004 SNO abstract (Berk).
IV. Open Trials Update:
| Study | Date Opened | Accrual (6/15/2004) | Monthly Accrual Rate (in past 6 months) | Protocol Projected Monthly Accrual | Expected Closure |
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| 0215 | 1/3/2003 | 66/332 | 6 | | February, 2008 |
| 0123 | 6/4/2003 | 9/205 | 1.3 | 12 | September, 2016 |
| 0315 | 12/5/2003 | 29/226 | 4.6 | 10 | January, 2008 |
| 0127 | 10/5/2001 | 39 | ECOG Trial | | |
| 0122 | 12/6/2002 | 355/468 | 27.3 | 30 | October, 2004 |
Dr. William Small presented potential amendments to RTOG 0123 (Captopril for prevention of late lung toxicity). These included standardization of blood draws, standardization of 3-D planning volume definitions, allowance for the use of Amifostine, allowance for the use of surgery, and allowance for participating on the PCI RTOG protocol.
V. Protocols with NCI Reviews:
RTOG 0326 - Ginseng for Radiation Fatigue: NCI has approved a two-arm phase III concept of 800 mg Ginseng Panax extract vs. placebo. The protocol is in preparation by Jackie Fisher.
RTOG 0226 - Celecoxib for the prevention of H&N second primaries: NCI has approved this concept, now with Phizer providing drug. Dr. Sidhu is drafting the full protocol, and is in discussion with TRP committee as to which biomarkers to consider for a correlative analysis.
VI. Protocol Concepts:
a. Head and Neck Mucositis:
Two phase III trials are in concept development, and were also approved favorably by the H&N committee – (Gelclair oral rinse vs. placebo for postoperative H&N irradiation (PI Dr. Kachnic), and Keratinocytic Growth Factor vs. placebo for locally advanced H&N cancer (PI Dr. Rosenthal). Drs. Kachnic and Rosenthal will work closely together to further develop these phase III protocols using similar eligibility (also allowing for IMRT, chemotherapy and feeding tubes), similar endpoints (pain and grade3+ mucositis), as well as similar assessment tools (CTC v3.0, VNA, BPI & patient-reported symptoms). While the Gelclair will have pain as the primary endpoint, the KGF trial is required to choose incidence of grade3+ mucositis for potential FDA approval of the drug if this endpoint proves positive. Drs. Berk and Bruner discussed also statistically powering the KGF trial for patient-reported pain as to avoid any potential “disconnects” with future results. Dr. List will assist in choosing the symptom assessment instrument. Separate QOL instruments will not be used. Both concepts were received quite favorable by the audience. Draft protocols will be presented to RTOG for statistics, and will then be sent for NCI review.
Dr. Berk presented work from the National Institute of Dental and Craniofacial Research of the National Institutes of Health testing a lower dose Thalidomide mouth rinse as a treatment for aphthous ulcers. If the results are sufficiently promising, this may be taken forward by the RTOG in a trial for radiation mucositis.
B. Bone Metastases:
Two new concepts were presented (NCIC re-irradiation for bone metastases of 8 Gy in one fractions vs. 20 Gy in five fractions by Dr.Wu, and RT for non-operable cord compression with 30 Gy in 10 fractions vs. 45 Gy in 15 fractions by Dr. Kachnic for Dr. Regine). The re-irradiation trial was met with only moderate enthusiasm by the audience, because despite the findings of RTOG 9714, radiation oncologists were still not routinely using 8 Gy in a single fraction. The CCOP Research Strategy Committee and the RTOG Research Strategy Committee, however, strongly endorsed participation in this international trial led by the NCIC. Therefore, the protocol will be forwarded to the NCI for concept approval. Dr. Regine’s concept of a dose intensification trial for non-operable cord compression was also met with moderate enthusiasm. There was concern that it may be difficult to place an emergent cord compression case quickly enough on a trial. One suggestion was to allow for randomization after one or two treatments. Another concern was the safety of 45 Gy in 15 fractions. The consensus was for Dr. Regine to report his concept with some pilot data at the January 2005 meeting, and/or reduction of the investigational RT dose to 42 Gy. In the interim, a survey of RTOG PI’s may be done to determine whether 42 or 45 Gy would be acceptable.
Two existing concepts were also reviewed. The first was the phase III proposal from Dr. Seider regarding patients with lung, breast or prostate bone metastases to be randomized to bisphosphonates or biphosphonates and a radionuclide (Samarium or Strontium). The draft concept is written and will be forwarded for statistical review, followed by NCI proposal review. Dr. Roach has had further discussion with Amgen Pharmaceuticals regarding his phase III concept for patients with high-risk prostate cancer as defined by a rapidly rising PSA after treatment or poor pre-treatment prognostic factors (PSA, Gleason Score and stage). These patients are to be started on hormone ablation (stratified by short vs. long duration) and then be randomized to an osteoclastic receptor antibody (AMG 162) administered subcutaneously vs. placebo. Issues of hormone ablation duration were discussed as well as correlative molecular studies to potentially predict skeletal response. The endpoints include rate of skeletal events, and the development of osteoporosis. Dr. Roach was instructed to prepare a draft concept for statistical review.
C. Radiation Xerostomia:
Dr. Berk presented a new concept of Yohimbine and Pilocarpine therapy for the prevention of radiation xerostomia in patients receiving therapy for H&N cancers. Concerns were raised regarding the safety of Yohimbine in women. Dr Berk was asked to collect toxicity data, and then re-present the concept to the group.
D. Neurocognitive Function:
Dr. Berk reviewed a phase III concept on the effect of Concerta (a once-daily form of Methylphenidate) on maintaining neurocognitive function for advanced GBM patients. Concerns were raised this patient population was unlikely to be seen by the radiation oncologist because of their extremely poor performance status. It was suggested patients with recurrent GBM be considered as the target population for this trial (as there are little effective treatments). The audience was in agreement, and therefore Dr. Berk will draft this concept for statistical review.
E. Skin Desquamation:
A new phase III concept of calendula ointment vs. physician preference was presented by Dr. Berk. He reported on the positive findings from a recently completed French study examining the efficacy of this cream to prevent breast skin toxicity in patients receiving adjuvant whole breast radiation. This trial used stratification based on bra size and BMI to define large breasted women (who often have an increased rate of skin morbidity). The audience was in favor of this concept but raised the importance of quantifying the amount of product used, as well as assuring patient compliance with the cream. Dr. Berk commented RTOG should develop a skin toxicity scale that would be sensitive to changes for women of color. Pain would be considered as the primary endpoint for this trial. Dr. Okunieff then presented a concept of curcumin (yellow coloring of curry) for the prevention of radiation dermatitis with breast irradiation. Animal hindleg experiments showed excellent prevention of skin reaction with oral or IV administration, without tumor protection. The Rochester CCOP has already opened this trial using 500 mg PO BID of the agent vs. placebo. Dr. Berk will work with Drs. Okunieff and Morrow to further develop a prevention trial, with the consideration of opening the curcumin trial through RTOG.
F. Acupuncture for the amelioration of male hot flashes in prostate cancer:
Dr. Johnstone from Emory University will be leading these efforts. A potential concept has been favorably approved at the GU Steering Committee and Research Strategy Committee. Drs. Berk, Bruner and Coyne will work with Dr. Johnstone to draft an acupuncture vs. sham concept with the potential for outside funding.
G. Depression:
Dr. Wheeler will work with Dr. Coyne to develop a prospective depression incidence study of head and neck patients with an interview component as to eliminate the potential for a “disconnect” between patient reported depressive symptoms and QOL measures.
VII. Late Effects:
Dr. Okunieff discussed the recent translational/late effects conference in Rochester with key presentations on the translation and validation of basic research being brought into the clinical setting (i.e. stem cell plasticity), as well as the issue of sensitivity for our current late effects scoring system (CTCAE v3.0).
VIII. High Priority Concepts to be Sent for NCI Review:
| Gelclair for mucositis protection | Kachnic & Rosenthal |
| KGF For mucositis protection | Rosenthal & Kachnic |
| NCIC for re-irradiation of bone mets | Chow & Hartsell |
| AMG 162 for high risk prostate cancer | Roach |
| Biphosphonates +/- radionuclides for bone mets | Seider |
| Acupuncture for hot flashes in prostate cancer | Johnston |
IX. Concepts Deferred but Active:
| Concerta for recurrent GBM | Berk |
| Re-irradiation for spinal cord compression | Regine |
| Prevention of breast dermatitis | Berk, Okunieff, White |
| Treatment of male osteoporosis | Lawton |
| Yohimbine & pilocarpine for xerostomia | Berk |
| BID radiation and Taxotere for palliation | Carracosa |
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Lawrence B. Berk, M.D., Ph.D., Chair
1. Introduction – Lawrence Berk, MD, Ph.D.
Dr. Berk reviewed the progress the Symptom Management Committee has made. RTOG 9714 a study for bone metastases has been completed and was presented as a plenary presentation at ASTRO in October of 2003. The manuscript will be submitted to New England Journal of Medicine next month. RTOG 9913 a study using Biafine® for Head and Neck erythema, an oral mucositis trial - RTOG 9901, and RTOG 0119 Melatonin for Brain Metastases were also completed, and analyses will be forthcoming.
Dr. Lisa Kachnic emphasized the need to build upon these trials with a logical progression into new trials addressing novel interventions for mucositis and bone metastases. An announcement was made that the CCOP renewal grant was due in the summer of 2004, and therefore, the rapid development of the aforementioned trials was of highest priority.
2. Drs. Kachnic and Berk reviewed the closed trials originating in Cancer Control or having cancer control credits. These include:
RTOG 9714 - Bone metastases.
RTOG 9801- Amifostine for lung cancer.
RTOG 9809 - PPS study.
RTOG 9901 - GM-CSF trial.
RTOG 9903 – Head & Neck erythropoietin trial.
RTOG 9913 - Biafine for Head & Neck.
RTOG 0119 - Melatonin for brain metastases.
3. Open trials originating in Cancer Control or having cancer control credits were then reviewed. These include:
RTOG 0122 - Juven for cancer cachexia.
RTOG 0123 - Captopril for lung toxicity.
RTOG 0214 - PCI for non-small cell lung cancer.
RTOG 0215 - Viagra for ED.
RTOG 0315 - Sandostatin for diarrhea.
4. One protocol has been revised and is being sent to the NCI for review:
RTOG 0326 Ginseng for radiation fatigue; NCI/Symptom management recommendations were made to change this trial into two arm phase III with a fixed ginseng dose; the revised protocol will be re-sent to NCI for review.
5. Proposed concepts were then reviewed:
A. Bone Metastases Trials
Two trials were discussed. Dr. Seider proposed a phase III trial for patients with lung, breast, or prostate bone metastases to be randomized to bisphosphonates or bisphosphonates and a radinuclide (Samarium or Strontium). Dr. Roach recommended a trial for patients with high-risk prostate cancer as defined by a rapidly rising PSAor < 2 asymptomatic bone metastases to be started on hormone ablation and then randomized to an osteoclastic receptor antibody (AMG 162) vs. conventional care. This audience received both concepts favorably, and draft protocols were requested.
B. Head & Neck Mucositis
Dr. Kachnic discussed a randomized phase III trial examining a proprietary oral rinse, Gelclair (OSI Pharmaceticals), for mucositis intervention and pain relief in postoperative head and neck cancers receiving radiation alone. OSI will provide drug and placebo. Dr. Kashyap from Amgen then presented a four arm randomized phase II drug scheduling concept put forth by Amgen pharmaceuticals in conjunction with Dr. Rosenthal from MD Anderson, examining recombinant Human Keratinizing Growth Factor for the reduction of oral mucositis in subjects with intermediate-locally advanced head and neck cancer receiving radiotherapy +/- chemotherapy. Both concepts were received favorably by this audience, as well as by the head and neck steering committee, and draft protocols were requested.
C. Radiation Xerostomia
Two acupuncture trials were presented. Dr. Streeter presented using classical needle-based acupuncture of hand meridians and ear meridians for the treatment of post radiation xerostomia. Dr. Wong presented the use of TENS based electro-acupuncture of foot and hand meridians to prevent radiation muscositis. Dr. Wong presented his preliminary data of the successful treatment of radiation xerostomia with his technique. It is hoped to set up an acupuncture subcommittee, with the addition of Dr. Peter Johnson, to bring forward the acupuncture trials into clinical sites. Dr. Wynn then presented a concept for the prevention of radiation xerostomia in head and neck patients of a three-arm trial of pilocarpine vs. amifostine vs. combined pilocarpine and amifostine.
D. Late Lung Toxicity
A possible replacement concept for the on-going RTOG 0123 Captopril study was discussed by Dr. Kachnic, on behalf of Drs. Feigenberg and Movsas, examining the use of pentoxifylline to prevent or ameliorate late lung toxicity in patients who received radiation +/- chemotherapy for stage III non-small cell or limited-stage small cell lung cancer.
E. Neurocognitive Function
Dr. Berk reviewed a phase III concept on the effect of Concerta (a once-daily form of methylphenidate) on maintaining neurocognitive function for advanced GBM patients.
F. Urinary Frequency
Dr. Gwen Wyatt presented a concept on the use of saw palmetto for urinary hesitancy.
G. Depression
Dr. Weaver presented a prospective incidence concept to determine the rates of depression in cancer patients. Dr. Weaver was encouraged to proceed with this prior to developing a full study.
6. Chemoprevention:
RTOG 0226 a concept using Celecoxib for prevention of Head and Neck second primaries, is on hold, as Celecoxib will not be supplied for the study. There was a general approval by the committee and audience to consider changing the Cox 2 inhibitor to Vioxx.
7. Late Effects:
Dr. Okunieff provided a presentation regarding a new late effects program at the University of Rochester, with a future meeting announcement.
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Charles Scarantino, M.D., Ph.D., Chair
1. Introduction – Charles Scarantino, MD. Ph.D.
Dr. Scarantino reviewed the progress the Symptom Management Committee has made. RTOG 9714, for bone metastases has been completed and will be presented as a plenary presentation at ASTRO this year. The analysis of RTOG 9709, a study Pilocarpine for prevention of xerostomia, has been published. We have completed RTOG 9913, Biafine © for Head and Neck erythema. In addition we have completed two oral mucositis trials, RTOG 9601 and RTOG 9901.
Dr. Scarantino emphasized the need to build upon these trials and have a logical progression into new trials. We need to determine what the next trial for prevention of radiation xerostomia should be. We need to determine how to address mucositis, both oral and esophagitis. And we need to determine how to proceed in skin care.
2. Dr. Berk and Dr. Scott then reviewed the open trials originating in Cancer Control or having cancer control credits. These include:
RTOG 9903 - H&N erythropoietin trial
RTOG 0119 - Melatonin for brain metastases
RTOG 0122 - Juven for cancer cachexia
RTOG 0123 - Captopril for lung toxicity
RTOG 0214 - PCI for non-small cell lung cancer
RTOG 0215 - Viagra for ED
3. Two protocols are at NCI for review:
RTOG 0315 Sandostatin for diarrhea
RTOG 0326 Ginseng for radiation fatigue
4. Proposed Concepts were then reviewed.
A. Bone Metastases Trials
Two trials were discussed. Dr. Seider proposed a trial for patients with bone metastases to be randomized to bisphosphonates or bisphosphonates and a radinuclide such as Samarium. Dr. Berk recommended a follow-up trial to RTOG—to try to increase the complete response rate, using low dose Gemcitabine as a radiosensitizer. Dr. Hartsell, the PI on RTOG 9714 could not attend the meeting and a final decision was postponed until the concepts could be discussed with him.
B. Acupuncture Trials
Two acupuncture trials were presented. Dr. Streeter presented using classical needle-based acupuncture of hand meridians and ear meridians for the treatment of post radiation xerostomia. Dr. Wong presented the use of TENS based electro-acupuncture of foot and hand meridians to prevent radiation muscositis. Dr. Wong presented his preliminary data of the successful treatment of radiation xerostomia with his technique. Dr. Berk asked Dr. Streeter to discuss this further with Dr. Wong and other acupuncturists and develop a research plan. It is hoped to set up an acupuncture subcommittee chaired by Dr. Streeter to bring forward the acupuncture trials into clinical sites.
C. Radiation Xerostomia
Dr. Wynn presented a concept for the prevention of radiation xerostomia in head and neck patients of a three arm trial of Pilocarpine vs. Amifostine vs. combined Pilocarpine and Amifostine. The Amifostine would be given SQ. There was concern that physicians would be unwilling to accrue to a non-Amifostine arm. RTOG 9901 did accrue without Amifostine, as did RTOG 9913. Further, RTOG 9709 was a positive trial, and it is important to build upon our previous trials. Therefore a three arm trial is felt to be appropriate.
D. Radiation Cystitis
Dr. Berk reviewed the status of a trial of cranberry extract for radiation cystitis. The NCCAM had an RFP for cranberries and cystitis and Dr. Berk submitted for funding. He should know the results over the summer. Gwen Wyatt presented a concept of the use of saw palmetto for urinary hesitancy. A formal concept was requested.
E. Gelclair for Radiation Mucositis
Dr. Berk has asked Dr. Kachnic to lead the Gelclair for mucositis research. The trial was initially presented for use during head and neck radiation. The company, OSI Pharmaceuticals, has asked that it be considered for use during lung cancer irradiation. This concept will be submitted by Dr. Kachnic as a protocol.
F. Androgen supplementation for lung cancer patients was withdrawn by Dr. Berk as to low a priority.
G. Actiq for oral mucositis pain has been dropped by Dr. Berk due to design problems.
H. Thalidomide for Radiation Mucositis
Dr. Berk reviewed a conference held with the NIH’s Dental and Craniofacial Surgery Institute on cooperating to bring their oral mucositis research into clinical trials. The meeting was successful. The Institute is running a pilot of oral thalidomide mouthwash for BMT patients. If the pilot is successful we anticipate running a trial for head and neck patients.
I. Honey for Radiation Mucositis
Dr. Berk withdrew this protocol because it had too high of a giggle factor at the NCI.
J. Inhaled Steroids for Radiation Pneumoniti
Dr. Berk presented Dr. McGarry’s concept to use inhaled steriods to prevent radiation pneumonitis during radiation therapy. It was felt that more background information is needed and we will ask Dr. McGarry to supply this.
K. Lexapro to Prevent Depression During Head and Heck Radiation
Dr. Weaver presented using Lexapro during radiation therapy of head and neck cancer patients to prevent or improve the depression among these patients. He proposed randomizing non-depressed and mild/moderate depression to placebo or Lexapro and severe patients to receive Lexapro. There was concern that patients should be evaluated by a psychologist or psychiatrist if depression is to be treated. Some thought the depression surveys were sufficient. There was also concern about Radiation Oncologists treating severe depression. Dr. O’Mara of DCP stated that a prospective incidence trial could be run to determine the rates of depression in these patients. It should be submitted as a regular protocol. Dr. Weaver was encouraged to proceed with this prior to developing a full study.
5. Chemoprevention
A presentation was then made on RTOG 0226, Celebrex for prevention of Head and Neck second primaries. There was a general approval of the protocol as presented.
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Lawrence B. Berk, M.D., Ph.D., Chair
1) REORGANIZATION OF CCOP COMMITTEE
The first item discussed was whether the name of the Committee should be changed to the Symptom Management Committee. There is confusion within the members of the RTOG as to what type of protocols are appropriate for the CCOP Committee. To clarify this, Dr. Berk suggested that the CCOP Committee be broken into two parts. One will be the CCOP Institutions Committee, which will deal with issues relevant to the functioning of the CCOP’s within the RTOG. This Committee would have the same Chair as the present CCOP Committee and would continue to meet during the Cancer Control Session. The Symptom Management Committee would, at least presently, have the same Chair as the CCOP Committee (and the proposed CCOP Institutions Committee) and the Committee would focus on symptom management trials. It would continue to meet during Cancer Control Session. Thus there would be four Committees under the aegis of Cancer Control: Symptom Management, CCOP Institutions, Chemoprevention and Late Effects.
The suggestion was put to a show of hands and the change was supported by a clear majority of members. Therefore the change will be forwarded to the RTOG’s administrative wing for their approval.
2) CLOSED PROTOCOLS
RTOG 9901 - GM-CSF for prevention of radiation induced mucositis completed accrual and is collecting the final information before analysis begins.
RTOG 9801 - Amifostine for prevention for esophagitis during lung irradiation which has completed accrual and preliminary analysis is underway.
RTOG 9809 - PPS for prevention of radiation induced diarrhea closed early due to loss of drug/placebo support, and is undergoing analysis.
RTOG 9913 – Biafine ® for prevention of head and neck mucositis has completed accrual and is undergoing analysis.
RTOG 9714 - Bone metastases fractionation trial has completed accrual and is getting the final data prior to analysis.
3) OPEN PROTOCOLS
RTOG 9903 - Epogen for H&N patients with anemia has picked up accrual and is to undergo a marketing push by the manufacturer.
RTOG 0215 - Viagra for erectile dysfunction is open and accruing.
RTOG 0122 - Juven is open and waiting for centers to get IRB approval and bioimpedence units as needed.
RTOG 0119 - Melatonin for brain metastases is accruing well (this trial is from Integrative Oncology, a subcommittee of CCOP, but is open through the Brain Tumor Committee).
RTOG 0214 - PCI for non-small cell lung cancer is open through the Lung Cancer Committee but has QOL and will receive Cancer Control credits.
4) PROTOCOLS AT NCI
RTOG 0123 - Captopril for prevention of radiation pneumonitis has undergone what is expected to be its final revision and is to be resubmitted to the NCI within the next month.
5) PROTOCOL CONCEPTS
RTOG 1053 - Samarium and Disphosphonates for treatment/prevention of bone metastases. Dr. Sieder was encouraged to resubmit the concept in a final form so that it can begin being processed for initial submission to the NCI.
RTOG 0315 - Sandostatin for prevention of radiation-induced diarrhea is awaiting initial submission to the NCI. It should be submitted within a month.
RTOG 1066 - Ginseng for radiation induced fatigue is ready for initial submission to the NCI and should be submitted within the next 3 months.
RTOG DEVELOPING STUDY - Acupuncture for treatment of radiation induced xerostomia. Dr. Oscar Streeter presented the rationale for using acupuncture in this setting and a preliminary trial design. The Committee was polled by a show of hands and the consensus was to develop the concept. He was encouraged to submit a protocol concept sheet prior to the next meeting. The Integrative Oncology Committee will work with him in developing the study.
RTOG DEVELOPING STUDY - Androgen supplementation for men with lung cancer. Dr. Berk presented a concept of Androgen supplementation, such as testosterone gel, for men with anergia and undergoing radiation therapy for lung cancer. The basis for this, studies in AIDS patients on hypogonadal men and studies suggesting men with advanced lung cancer tend to be hypogonadal was discussed. The committee was polled with a show of hands and Dr. Berk was encouraged to continue development.
RTOG DEVELOPING STUDY- Transoral Fentanyl for treatment of radiation stomatitis. An extended discussion was led by Dr. Berk on a possible protocol for the use of transoral fentanyl (Actiq) for treatment of radiation stomatitis in head and neck cancer treatment. The rationale is a trial showing a Morphine Sulphate rinse and spit was superior to oral Morphine for this situation. A trial of rinse and spit Morphine seems impractical in a group-wide setting. Therefore Actiq could be a reasonable alternative. However, the endpoints and the design of the trial are not straightforward. The Committee decided to go forward with exploring this concept. Dr. Joseph Weaver volunteered to assist in the development of the study.
RTOG DEVELOPING STUDY - Cranberry pills for prevention of radiation cystitis. Somewhat sheepishly Dr. Berk mentioned that he used cranberry extract pills for radiation cystitis during prostate cancer treatment and has found that they seem to work well. He asked if any other centers are using cranberry for this. Several sites reported that they use cranberry juice and also believe that is efficacious. Dr. Berk explained that cranberry juice is high in calories so he prefers the pills. The Committee was polled and there was majority support for exploring a trial of cranberry pills for radiation cystitis. Dr. Berk will seek design support from the RA’s.
RTOG DEVELOPING STUDY – Dr. Raymond Wynn presented a protocol concept comparing subcutaneous Amifostine with subcutaneous Amifostine and oral Pilocarpine. A poll of the Committee showed that a majority supported proceeding with this development of this concept. This topic has been discussed at previous meetings and he was encouraged to move forward with a protocol concept sheet.
6) AREAS NEEDING PROTOCOLS
Some of the areas that need protocols are Head and Neck Mucositis, Xerostomia prevention and Radiation proctitis prevention and treatment.
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