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

Sponsor

Genta Incorporated (Industry)

Overall Status

Completed

CT.gov ID

NCT00016263

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: oblimersen sodium Drug: dacarbazine	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2000

Actual Study Completion Date :

Dec 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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