Title

A Phase III, Randomized Trial of Surgical Resection with or without BCG versus Best Medical Therapy as Initial Treatment in Stage IV Melanoma

Purpose

The purpose of this Phase III study is to understand if surgery as a first treatment for Stage IV melanoma will lengthen the time to disease recurrence (comes back) or progression (gets worse) compared to non surgical (medical) therapy.

Additionally, the study is expected to help us better understand the usefulness of BCG in boosting anti tumor reactions and of monitoring disease and/or therapy using various markers.

Eligibility

Inclusion:

• Age 18 or over and have a minimum life expectancy (excluding melanoma) of 5 years

• All known disease must be surgically resectable in the opinion of a participating surgeon.

• Patients 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.

• ECOG of 0-1

• Patients may have up to 3 visceral organs involved. Any number of lesions up to 6 is allowed.

• Subjects must be willing and able to comply with the protocol.

• Must have adequate Blood levels and organ function

Exclusion:

• Unresectable metastatic disease or more than 4 months since stage IV diagnosis.

• Known Brain or Spinal Chord tumor involvement or bone metastasis

• History of primary uveal or mucosal melanoma.

• Another concomitant diagnosis that limits life expectancy to less than 5 years or 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.

• Women who are breastfeeding or pregnant

• Serious cardiac, gastrointestinal, hepatic or pulmonary disease that would make surgical resection high-risk.

• 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.

Treatment

If you are eligible for the study, you will be randomly assigned to one of the study groups described below. You will not have any choice as to which arm of the study you enter.

If you are randomly assigned to the best medical therapy group, you will not initially undergo surgery, but you will be treated with the therapy that your medical oncologist or surgeon feels is best for you. This treatment may include standard or experimental therapies.

If you are randomly assigned to the surgery plus observation group, you will undergo complete resection (surgical removal) of all known disease, if possible. After surgery, you will be followed regularly and monitored for disease recurrence.

If you are randomly assigned to the surgery plus adjuvant (added) BCG group, you will first have a complete resection (surgical removal) of all known disease, if possible. After you have recovered from your surgery, you will be given two doses of BCG two weeks apart. Each dose is given as 8 separate injections into the skin (called intradermal injections). BCG stands for Bacillus Calmette Guerin and is being tested in this study to determine whether it stimulates or boosts your immune system.