Abraxane and Temodar Plus Genasense in Advanced Melanoma

Study Overview
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Brief Summary
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This study is designed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of combination treatment with Temodar®, Genasense®, and Abraxane® in chemotherapy-naïve subjects with advanced melanoma and normal lactate dehydrogenase (LDH).

Official Title
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A Pilot Study of Abraxane® (Albumin-bound Paclitaxel) and Temodar® (Temozolomide) Plus Genasense® (Oblimersen Sodium) in Subjects With Advanced Melanoma (The ATG Study).

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Genasense® (oblimersen)
* Drug: Abraxane® (paclitaxel protein-bound particles for injectable suspension)
* Drug: Temodar® (temozolomide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with progressive, unresectable, or advanced melanoma who are considered to be candidates for systemic treatment with chemotherapy Subjects will have measurable disease, an Eastern Cooperative Oncology Group Performance Status less than or equal to 2, and serum LDH less than or equal to 1.1 times the upper limit of normal, but will not have previously received cytotoxic chemotherapy Prior immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy is permitted in the adjuvant and/or metastatic setting Exclusion Criteria: Prior treatment with cytotoxic chemotherapy, including regional perfusion, or with Genasense®(oblimersen sodium)Injection Nonmeasurable disease only History or presence of brain metastasis or leptomeningeal disease Significant medical disease other than cancer Known human immunodeficiency virus infection Pregnant or lactating Known hypersensitivity to temozolomide, phosphorothioate-containing oligonucleotides, or products containing human albumin Use of any experimental therapy within 3 weeks prior to baseline evaluations, Other anticancer treatment (such as chemotherapy, radiation, or biologic or investigational therapies) while receiving therapy in this study

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Genasense® (oblimersen)|Cohorts 1 and 2: Genasense 7 mg/kg/day by continuous intravenous infusion beginning on Day 1 and continuing for 7 days (Week 1) and beginning again on Day 22 and continuing for 7 days (Week 4); Cohort 3: Genasense 900 mg as a 1-hour intravenous infusion on Day 1, 4, 8, and 11 (Weeks 1 and 2) and Day 22, 25, 29, and 32 (Weeks 4 and 5).|
|Drug: Abraxane® (paclitaxel protein-bound particles for injectable suspension)|Cohorts 1 and 2: Abraxane 175 mg/m2 or 260 mg/m2 as a 30-minute intravenous infusion on Day 8 and Day 29 following end of Genasense continuous infusion; Cohort 3: Abraxane 175 mg/m2 as a 30-minute intravenous infusion on Day 4 and Day 25 following end of Genasense 1-hour infusion|
|Drug: Temodar® (temozolomide)|Cohorts 1-3: Temodar 75 mg/m2/day orally on Days 1 through 42 (Week 1 through Week 6)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety based on adverse event reports and clinical laboratory findings |  | During protocol therapy prior to the start of and during each cycle and up to 30 days after last dose of protocol therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (including rate of complete response) |  | At the end of each cycle during protocol therapy, with follow-up every 2 months for up to 2 years from date of registration | 
| Duration of response (including the rate of durable response) |  | At the end of each cycle during protocol therapy, with follow-up every 2 months for up to 2 years from date of registration | 
| Time to disease progression |  | At the end of each cycle during protocol therapy, with follow-up every 2 months for up to 2 years from date of registration | 
| Incidence of brain metastasis |  | At the end of each cycle during protocol therapy, with follow-up every 2 months for up to 2 years from date of registration | 
| Survival |  | 12,15, and 18 months from date of registration, with follow-up every 2 months for up to 2 years from date of registration | 
| Correlations of drug concentrations, intracellular Bcl-2 content, and response |  | Cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Melanoma, Normal baseline LDH, Chemotherapy naive