Stage IV Surgery Versus Best Medical Therapy

NCT01013623 | Terminated Phase 3 DMC

• 2 other identifiers: MORD-STG4SURG-04093P01CA012582-35S1
• Study Type: interventional
• Target: 12
• Locations: 5 countries
• Sites: 19

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.

Conditions

Stage IV Resectable Melanoma

Keywords

melanoma; stage IV; resectable; surgery; medical therapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Defined as time from randomization to death from any cause

  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 (3)

• 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.

• 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.

• 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.

Study Arms (3)

Best Medical Therapy

ACTIVE COMPARATOR

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

Surgery Alone

ACTIVE COMPARATOR

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

Surgery + BCG

ACTIVE COMPARATOR

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

Interventions

Surgery PROCEDURE

surgical resection to remove all known disease

Surgery Alone

Surgery plus 2 adjuvant doses of BCG PROCEDURE

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.

Surgery + BCG

best medical therapy OTHER

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.

Best Medical Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• WBC \>3,000/mm3
• Lymphocytes \>800/mm3
• Platelets \>100,000/mm3
• Creatinine \<2.0 mg/dL
• Bilirubin \<2.0 mg/dL

You may not qualify if:

• 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

Sponsors & Collaborators

• Saint John's Cancer Institute: lead
• Melanoma Research Alliance: collaborator

Study Sites (19)

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Buffalo General Hospital

Buffalo, New York, 14203, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Penn State Hershey Cancer Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Geisinger Clinic

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Main Line Health System

Wynnewood, Pennsylvania, 19096, United States

Location

Dallas Surgical Group

Dallas, Texas, 75235, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75390-9155, United States

Location

IHC Cancer Services Intermountain Healthcare

Murray, Utah, 84157, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4101, Australia

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 94239, Israel

Location

Istituto Nazionale dei Tumori Napoli

Naples, 80121, Italy

Location

Univesitair Medisch Centrum Groningen

Groningen, 9700 RB, Netherlands

Location

MeSH Terms

Conditions

Melanoma

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Donald L. Morton, MD

  Saint John's Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2009
• First Posted: November 16, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: September 26, 2012

Record last verified: 2012-09

Locations

US (15); AU (1); IL (1); IT (1); NL (1)