Stage IV Surgery Versus Best Medical Therapy (STG4SURG)
Stage IV Resectable Melanoma
Procedure: Surgery plus 2 adjuvant doses of BCG
Other: best medical therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase III, Randomized Trial of Surgical Resection With or Without BCG Versus Best Medical Therapy as Initial Treatment in Stage IV Melanoma|
- Overall survival [ Time Frame: 3 interim analyses will be conducted when 75, 148, and 217 events (deaths) have occurred. The final analysis will be conducted when all 284 expected events have occurred. ] [ Designated as safety issue: No ]Defined as time from randomization to death from any cause
- Time to progression of initial metastatic sites (progression-free survival) [ Time Frame: 3 interim analyses will be conducted when 75, 148, and 217 primary events have occurred. The final analysis will be conducted when all 284 expected events have occurred. ] [ Designated as safety issue: No ]For this study, PFS is defined as the time from randomization to disease recurrence at initial metastatic site in patients rendered disease-free by surgery, or time from randomization to RECIST-defined progression of target lesions in patients receiving best medical therapy or those having residual disease following surgery.
- Melanoma-specific survival [ Time Frame: 3 interim analyses will be conducted when 75, 148, and 217 recurrences/progressions have occurred. The final analysis will be conducted when all 284 expected events have occurred. ] [ Designated as safety issue: No ]Defined as time from randomization to death due to melanoma. Death due to causes other than melanoma are not considered events for this analysis.
- Time to development of new metastatic sites. [ Time Frame: 3 interim analyses will be conducted when 75, 148, and 217 primary events have occurred. The final analysis will be conducted when all 284 expected events have occurred. ] [ Designated as safety issue: No ]This endpoint is defined as the time from randomization to disease recurrence at new metastatic sites in patients rendered disease-free by surgery, or time from randomization to the development of new metastatic sites of disease in patients in the best medical therapy group. Progression of existing lesions in the best medical therapy arm will not be considered an event for this endpoint.
|Study Start Date:||November 2009|
|Study Completion Date:||September 2012|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Best Medical Therapy
The best medical therapy group will not initially undergo surgery, but will be treated with the therapy that medical oncologists or surgeons feel is best for the patient. This treatment may include standard or experimental therapies.
Other: best medical therapy
Patients randomized to the Best Medical Therapy arm will decide on a course of medical therapy based on what the patient's medical oncologists feels is best for the patient. Best systemic medical therapy may include clinical trials of new agents or standard non-protocol treatments. Patients who progress on the best medical treatment arm may switch to a different medical therapy or, if still appropriate, may receive surgery.
Active Comparator: Surgery Alone
The surgery alone group will undergo complete resection (surgical removal) of all known disease, if possible. After surgery, patients will be followed regularly and monitored for disease recurrence.
surgical resection to remove all known disease
Active Comparator: Surgery + BCG
The Surgery + BCG group will first have a complete resection (surgical removal) of all known disease, if possible. After recovery from surgery, two doses of BCG will be given two weeks apart. Each dose is given as 8 separate injections into the skin (called intradermal injections).
Procedure: Surgery plus 2 adjuvant doses of BCG
Patients in the surgical resection + BCG arm will have an additional two visits to receive BCG. The first dose of BCG will be given no earlier than 4 weeks after surgery, and the second BCG dose will follow 2 weeks later. The actual doses are determined by the patient's pre-study tuberculin-reactivity status. Patients with a pre-study PPD induration of ≥10 mm will be given half the normal dose of BCG. Those with PPD induration of ≥20 mm will be given 25% of the normal dose.
This study is designed to examine the impact of surgical resection versus medical therapy as initial treatment therapy for patients with Stage IV melanoma. Surgical resection is thought to be efficacious in highly selected patients with solitary metastases, but not in patients with multiple sites of metastases. Even in those with solitary metastases, there is considerable debate among major melanoma centers over whether undergoing initial systemic medical therapy prior to surgical resection should be preferred to initial surgical resection upon Stage IV diagnosis. According to Dr. Dan Coit, Co-leader of the Melanoma Disease Management Team at Memorial Sloan Kettering Cancer Institute in New York, a trial of initial medical therapy is their standard approach on the multidisciplinary melanoma service even for patients with solitary distant metastases (personal communication, 15 Dec 2009).
Many who favor upfront medical therapy believe that delay before surgical resection may avoid unnecessary surgery by identifying patients who progress early due to the outgrowth of occult metastases at multiple sites, which may make the patient unresectable.
This is a Phase III, randomized, international, multicenter study of metastasectomy with or without BCG versus best medical therapy as initial therapy in Stage IV melanoma. This study has three arms: surgical resection plus BCG as an immune adjuvant, surgical resection plus observation, and best medical therapy (BMT). Since no systemic medical therapy has been demonstrated to be superior to DTIC and multiple new therapies are being evaluated, the choice as to what constitutes best medical therapy will be determined by the individual investigator based on the standard of care for systemic medical therapy at that particular multicenter site. Best systemic medical therapy may include clinical trials of new agents or standard non-protocol treatments (e.g., DTIC or Temodar according to the standard of care at the multi-center site).
Patients who progress on the best medical treatment arm may switch to a different medical therapy or, if appropriate, have surgical therapy; similarly, surgery patients may have additional surgical resection or receive medical therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01013623
|United States, California|
|UC Davis Medical Center|
|Sacramento, California, United States, 95817|
|John Wayne Cancer Institute|
|Santa Monica, California, United States, 90404|
|United States, Illinois|
|Chicago, Illinois, United States, 60612|
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Buffalo General Hospital|
|Buffalo, New York, United States, 14203|
|United States, North Carolina|
|Wake Forest University|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|Penn State Hershey Cancer Center|
|Hershey, Pennsylvania, United States, 17033|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Wilkes-Barre, Pennsylvania, United States, 18711|
|Main Line Health System|
|Wynnewood, Pennsylvania, United States, 19096|
|United States, Texas|
|Dallas Surgical Group|
|Dallas, Texas, United States, 75235|
|UT Southwestern Medical Center at Dallas|
|Dallas, Texas, United States, 75390-9155|
|United States, Utah|
|IHC Cancer Services Intermountain Healthcare|
|Murray, Utah, United States, 84157|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States, 84112|
|Princess Alexandra Hospital|
|Brisbane, Queensland, Australia, 4101|
|Tel-Aviv Sourasky Medical Center|
|Tel-Aviv, Israel, 94239|
|Istituto Nazionale dei Tumori Napoli|
|Naples, Italy, 80121|
|Univesitair Medisch Centrum Groningen|
|Groningen, Netherlands, 9700 RB|
|Study Chair:||Donald L. Morton, MD||John Wayne Cancer Institute|