Clinical trial NCT01013623: Stage IV Surgery Versus Best Medical Therapy
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Stage IV Resectable Melanoma
Keywords: melanoma
stage IV
resectable
surgery
medical therapy
Lead sponsor: Saint John's Cancer Institute
Sponsor class: OTHER
Collaborators: name: Melanoma Research Alliance
First posted: 2009-11-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Patients must provide informed written consent for participation.
* At least 18 years of age
* Have a minimum life expectancy (excluding melanoma) of 5 years.
* All known disease must be surgically resectable in the opinion of a participating surgeon.
* 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.
* Up to 3 visceral organs involved
* Up to 6 lesions allowed
* Must have ECOG performance status of 0 or 1.
* 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.
* Laboratory values within 30 days of randomization:

  1. WBC \>3,000/mm3
  2. Lymphocytes \>800/mm3
  3. Platelets \>100,000/mm3
  4. Creatinine \<2.0 mg/dL
  5. Bilirubin \<2.0 mg/dL
  6. Alkaline phosphatase \< 2X upper limit of normal (ULN)
  7. SGOT \< 2X ULN
  8. SGPT \< 2X ULN
  9. LDH \< 1.5X ULN

Exclusion Criteria:

* 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

Primary outcomes:
measure: Overall survival
timeFrame: 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.
Secondary outcomes:
measure: Time to progression of initial metastatic sites (progression-free survival)
timeFrame: 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.
measure: Melanoma-specific survival
timeFrame: 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.
measure: Time to development of new metastatic sites.
timeFrame: 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.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Buffalo
country: United States
facility: Buffalo General Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Wynnewood
country: United States
facility: Main Line Health System
state: Pennsylvania
city: Dallas
country: United States
facility: Dallas Surgical Group
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Murray
country: United States
facility: IHC Cancer Services Intermountain Healthcare
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Naples
country: Italy
facility: Istituto Nazionale dei Tumori Napoli
city: Groningen
country: Netherlands
facility: Univesitair Medisch Centrum Groningen
Study officials:
affiliation: Saint John's Cancer Institute
name: Donald L. Morton, MD
role: STUDY_CHAIR
References: