Randomized Study Of Dacarbazine Versus Dacarbazine Plus G3139 (Bcl-2 Antisense Oligonucleotide) In Patients With Advanced Malignant Melanoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant melanoma

- Progressive disease that is unresectable or metastatic

- No primary ocular or mucosal melanoma

- At least 1 unidimensionally measurable lesion by physical exam or imaging studies

- At least 10 mm by caliper for superficial cutaneous disease

- At least 20 mm by contrast-enhanced or spiral CT scan for visceral or nodal/soft
tissue disease

- No bone metastases as only site of measurable disease

- Lesions considered non-measurable include the following:

- Bone lesions

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging

- Lesions located in a previously irradiated area

- No brain metastases or leptomeningeal disease

- Considered a medical candidate for dacarbazine treatment

PATIENT CHARACTERISTICS:

Age:

- Any age

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8 g/dL (hematopoietic growth factor or transfusion independent)

Hepatic:

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- ALT/AST no greater than 2.5 times ULN

- Alkaline phosphatase no greater than 2.5 times ULN

- Albumin at least 2.5 g/dL

- PT/PTT no greater than 1.5 times ULN

- No history of chronic hepatitis or cirrhosis

Renal:

- Creatinine no greater than 1.5 times ULN OR

- Creatinine clearance at least 50 mL/min

Cardiovascular:

- No uncontrolled congestive heart failure

- No New York Heart Association class III or IV disease

- No symptomatic coronary artery disease (e.g., uncontrolled arrhythmias or recurrent
chest pain despite prophylactic medication)

- No cardiovascular signs and symptoms at least grade 2 within the past 4 weeks

Other:

- Intellectually, emotionally, and physically able to maintain an ambulatory infusion
pump

- Satisfactory venous access

- No other significant medical disease

- No uncontrolled seizure disorder

- No active infection

- No uncontrolled diabetes mellitus

- No active autoimmune disease

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- No known hypersensitivity to phosphorothioate-containing oligonucleotides or
dacarbazine

- No known HIV infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior immunotherapy, cytokine, biologic, or vaccine therapy in
the adjuvant and/or metastatic setting and recovered

- No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF], sargramostim
[GM-CSF] or epoetin alfa) during course 1 of study

Chemotherapy:

- No prior cytotoxic chemotherapy, including regional perfusion

Endocrine therapy:

- No concurrent chronic corticosteroids with an average dose of at least 20 mg of
prednisone or equivalent per day

Radiotherapy:

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

- No prior radiotherapy to measurable target lesions unless progression occurred at
that site or measurable disease developed outside the treated area

Surgery:

- At least 4 weeks since prior surgery and recovered

- No prior organ allografts

Other:

- At least 3 weeks since prior experimental therapy

- No prior intratumoral injection therapy to measurable target lesions unless
progression occurred at that site or measurable disease developed outside the treated
area

- No concurrent immunosuppressive drugs

- No concurrent anticoagulation therapy except 1 mg/day of warfarin for central line
prophylaxis