Stage IV Surgery Versus Best Medical Therapy

NCT ID: NCT01013623

Last Updated: 2012-09-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2012-09-30

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.

Conditions

Stage IV Resectable Melanoma

Keywords

melanoma; stage IV; resectable; surgery; medical therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

best medical therapy

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Surgery

Intervention Type: PROCEDURE

surgical resection to remove all known disease

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).

Group Type: ACTIVE_COMPARATOR

Surgery plus 2 adjuvant doses of BCG

Intervention Type: 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.

Interventions

Surgery

surgical resection to remove all known disease

Intervention Type: 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.

Intervention Type: PROCEDURE

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Melanoma Research Alliance

OTHER

Sponsor Role: collaborator

Saint John's Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald L. Morton, MD

Role: STUDY_CHAIR

Saint John's Cancer Institute

Locations

UC Davis Medical Center

Sacramento, California, United States

John Wayne Cancer Institute

Santa Monica, California, United States

Rush University

Chicago, Illinois, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Buffalo General Hospital

Buffalo, New York, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Penn State Hershey Cancer Center

Hershey, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Geisinger Clinic

Wilkes-Barre, Pennsylvania, United States

Main Line Health System

Wynnewood, Pennsylvania, United States

Dallas Surgical Group

Dallas, Texas, United States

UT Southwestern Medical Center at Dallas

Dallas, Texas, United States

IHC Cancer Services Intermountain Healthcare

Murray, Utah, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Istituto Nazionale dei Tumori Napoli

Naples, , Italy

Univesitair Medisch Centrum Groningen

Groningen, , Netherlands

Countries

United States; Australia; Israel; Italy; Netherlands

Other Identifiers

3P01CA012582-35S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MORD-STG4SURG-0409

Identifier Type: -

Identifier Source: org_study_id