Dacarbazine With or Without Oblimersen (G3139) in Treating Patients With Advanced Malignant Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen (G3139) may help dacarbazine kill more cancer cells by making tumor cells more sensitive to the drug. It is not yet known if dacarbazine is more effective with or without oblimersen (G3139). PURPOSE: Randomized phase III trial to compare the effectiveness of dacarbazine with or without oblimersen (G3139) in treating patients who have advanced malignant melanoma.

Detailed Description
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OBJECTIVES: Compare the survival of patients with advanced malignant melanoma treated with dacarbazine with or without oblimersen (G3139). Compare the response rate, durable response rate, and progression-free survival of patients treated with these regimens. Compare the safety of these regimens in this patient population. Compare the performance status, body weight, and tumor-related symptoms of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1 or 2), extent of metastases and lactate dehydrogenase (LDH) level (skin subcutaneous and/or lymph node metastases without visceral involvement and normal LDH vs any visceral metastases or elevated LDH), and liver metastases (yes vs no). Patients are randomized to one of two treatment arms. Arm I: Patients receive dacarbazine IV over 60 minutes on day 1. Arm II: Patients receive oblimersen (G3139) IV continuously over days 1-6 followed by dacarbazine IV over 60 minutes on day 6. Treatment repeats every 21 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response may be eligible for another 8 courses of treatment in an extension protocol. Patients are followed at least every 2 months for up to 2 years after study. PROJECTED ACCRUAL: A total of 750 patients (375 per arm) will be accrued for this study.

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

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: oblimersen sodium
* Drug: dacarbazine


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: oblimersen sodium|nan|
|Drug: dacarbazine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III melanoma, stage IV melanoma, recurrent melanoma