Stage IV Surgery Versus Best Medical Therapy
- Conditions
- Stage IV Resectable Melanoma
- Interventions
- Other: best medical therapyProcedure: SurgeryProcedure: Surgery plus 2 adjuvant doses of BCG
- Registration Number
- NCT01013623
- Lead Sponsor
- Saint John's Cancer Institute
- Brief Summary
This study will establish the role of surgical versus nonsurgical approaches in patients whose melanoma has spread to distant sites. Results will help clinicians develop a standardized initial approach that prolongs survival and optimizes quality of life. Results also will indicate whether Bacillus Calmette-Guerin (BCG) postoperative immunotherapy significantly improves the outcome of patients treated with surgery.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
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Patients must provide informed written consent for participation.
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At least 18 years of age
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Have a minimum life expectancy (excluding melanoma) of 5 years.
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All known disease must be surgically resectable in the opinion of a participating surgeon.
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Must have a histologic diagnosis of Stage IV melanoma arising from a primary cutaneous site or visceral metastasis from an unknown primary site and be within 4 months of initial stage IV diagnosis.
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Up to 3 visceral organs involved
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Up to 6 lesions allowed
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Must have ECOG performance status of 0 or 1.
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Must be in good general health with no serious co-morbid illness. Good clinical judgment must be exercised in careful selection of patients who are candidates for surgical resection of distant metastases.
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Laboratory values within 30 days of randomization:
- WBC >3,000/mm3
- Lymphocytes >800/mm3
- Platelets >100,000/mm3
- Creatinine <2.0 mg/dL
- Bilirubin <2.0 mg/dL
- Alkaline phosphatase < 2X upper limit of normal (ULN)
- SGOT < 2X ULN
- SGPT < 2X ULN
- LDH < 1.5X ULN
- Unresectable metastatic disease or more than 4 months since stage IV diagnosis.
- Brain or bone metastatic sites.
- History of primary uveal or mucosal melanoma.
- Another concomitant diagnosis that limits life expectancy to less than 5 years.
- Chronic immunosuppression due to inherited, acquired or iatrogenic immune defect. This includes active HIV, hepatitis, or use of immunosuppressive medications as a component of anti-rejection therapy for organ transplant, as treatment for an autoimmune disease.
- More than 3 involved visceral organ sites or more than 6 metastatic lesions.
- Psychiatric disorder or organic brain syndrome that might preclude participation in the protocol.
- Diagnosis of other malignancy in the past 5 years except adequately treated low grade malignancies such as basal cell carcinoma, cutaneous squamous cell carcinoma, carcinoma-in-situ of the cervix, or other neoplasm that will not limit life expectancy to less than 5 years.
- Serious cardiac, gastrointestinal, hepatic or pulmonary disease that would make surgical resection high-risk.
- Pregnancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Best Medical Therapy 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. Surgery Alone Surgery 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. Surgery + BCG Surgery plus 2 adjuvant doses of 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).
- Primary Outcome Measures
Name Time Method Overall survival 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. Defined as time from randomization to death from any cause
- Secondary Outcome Measures
Name Time Method Time to progression of initial metastatic sites (progression-free survival) 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. 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 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. 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. 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. 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.
Trial Locations
- Locations (19)
Dallas Surgical Group
🇺🇸Dallas, Texas, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Univesitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Tel-Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Istituto Nazionale dei Tumori Napoli
🇮🇹Naples, Italy
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Penn State Hershey Cancer Center
🇺🇸Hershey, Pennsylvania, United States
Rush University
🇺🇸Chicago, Illinois, United States
UT Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
John Wayne Cancer Institute
🇺🇸Santa Monica, California, United States
Buffalo General Hospital
🇺🇸Buffalo, New York, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Geisinger Clinic
🇺🇸Wilkes-Barre, Pennsylvania, United States
Main Line Health System
🇺🇸Wynnewood, Pennsylvania, United States
Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
IHC Cancer Services Intermountain Healthcare
🇺🇸Murray, Utah, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States