Stage IV Surgery Versus Best Medical Therapy (STG4SURG)

This study has been terminated.
(Lack of accrual, lack of continued funding.)
Sponsor:
Collaborator:
Melanoma Research Alliance
Information provided by (Responsible Party):
John Wayne Cancer Institute
ClinicalTrials.gov Identifier:
NCT01013623
First received: November 12, 2009
Last updated: September 24, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Stage IV Resectable Melanoma
Procedure: Surgery
Procedure: Surgery plus 2 adjuvant doses of BCG
Other: best medical therapy
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by John Wayne Cancer Institute:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 12
Study Start Date: November 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Procedure: Surgery
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01013623

Locations
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
Rush University
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
Geisinger Clinic
Wilkes-Barre, Pennsylvania, United States, 18711
Main Line Health System
Wynnewood, Pennsylvania, United States, 19096
United States, Texas
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-9155
Dallas Surgical Group
Dallas, Texas, United States, 75235
United States, Utah
IHC Cancer Services Intermountain Healthcare
Murray, Utah, United States, 84157
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4101
Israel
Tel-Aviv Sourasky Medical Center
Tel-Aviv, Israel, 94239
Italy
Istituto Nazionale dei Tumori Napoli
Naples, Italy, 80121
Netherlands
Univesitair Medisch Centrum Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
John Wayne Cancer Institute
Melanoma Research Alliance
Investigators
Study Chair: Donald L. Morton, MD John Wayne Cancer Institute
  More Information

No publications provided

Responsible Party: John Wayne Cancer Institute
ClinicalTrials.gov Identifier: NCT01013623     History of Changes
Other Study ID Numbers: MORD-STG4SURG-0409, 3P01CA012582-35S1
Study First Received: November 12, 2009
Last Updated: September 24, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by John Wayne Cancer Institute:
melanoma
stage IV
resectable
surgery
medical therapy

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 21, 2014