Trial of Dacarbazine With or Without Genasense in Advanced Melanoma

Study Overview
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Brief Summary
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This study is being performed to prospectively determine whether dacarbazine plus Genasense is significantly better than dacarbazine plus placebo in chemotherapy-naive patients with advanced melanoma and low baseline LDH (LDH less than or equal to 0.8 times the upper limit of normal). LDH is a biomarker strongly associated with improved outcomes in a recent trial of dacarbazine plus Genasense.

Official Title
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A Multicenter, Randomized, Double-blind Study of Dacarbazine With or Without Genasense in Chemotherapy-naive Subjects With Advanced Melanoma and Low LDH (The AGENDA Trial)

Conditions
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Melanoma

Intervention / Treatment
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* Drug: dacarbazine plus Genasense
* Drug: dacarbazine plus placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of melanoma Progressive disease that is not surgically resectable, or metastatic Stage IV Low-normal LDH, defined as ≤ 0.8 times the upper limit of normal No prior chemotherapy Measurable disease ECOG performance status ≤ 1 At least 4 weeks and recovery from effects of major prior surgery or other therapy, including immunotherapy, radiation therapy, or cytokine, biologic or vaccine therapy Prior immunotherapy allowed Adequate organ function Exclusion Criteria: Prior cytotoxic chemotherapy, including regional perfusion, or prior Genasense treatment Primary ocular or mucosal melanoma Bone-only metastatic disease History or presence of brain metastasis or leptomeningeal disease Significant medical disease other than cancer Organ allograft

Ages Eligible for Study
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Minimum Age: 18 Years

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
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Dacarbazine with Genasense | Drug: dacarbazine plus Genasense<br>* Protocol therapy will be administered in 21-day cycles for up to 8 cycles. Subjects in the dacarbazine plus Genasense group will receive Genasense 7 mg/kg/day by continuous intravenous infusion beginning on Day 1 and continuing for 5 days (120 hours) plus dacarbazine 1000 mg/m2 as a 60-minute intravenous infusion immediately following the conclusion of the Genasense infusion. Subjects who are responding or have stable disease after 8 cycles of therapy may, at the Investigator's discretion, continue that same therapy for up to 8 additional cycles.<br>* Other names: dacarbazine plus Genasense (oblimersen, G3139);|
| Active Comparator: B<br>Dacarbazine with placebo | Drug: dacarbazine plus placebo<br>* Protocol therapy will be administered in 21-day cycles for up to 8 cycles. Subjects in the dacarbazine plus placebo group will receive placebo (that is, locally available commercial 0.9% Sodium Chloride Injection) by continuous intravenous infusion beginning on Day 1 and continuing for 5 days (120 hours) plus dacarbazine 1000 mg/m2 as a 60-minute intravenous infusion immediately following the conclusion of the placebo infusion. Subjects who are responding or have stable disease after 8 cycles of therapy may, at the Investigator's discretion, continue that same therapy for up to 8 additional cycles.<br>* Other names: dacarbazine plus placebo (0.9% Sodium Chloride Injection);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival and overall survival |  | Every 42 days from date of randomization during protocol therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate, durable response rate, duration of response, safety |  | Response and progression every 42 days from date of randomization during protocol therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Advanced Melanoma, Malignant Melanoma, Metastatic Melanoma, Skin Cancer, Genasense, oblimersen, antisense, Bcl-2 antisense, G3139, dacarbazine