Safety and Efficacy Study of a New Chemotherapy Agent to Treat Metastatic Melanoma

Study Overview
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Brief Summary
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Primary objective: To evaluate the efficacy of two different dosing schedules of MS-275 in subjects with metastatic melanoma Secondary objectives: To evaluate the safety and to assess the pharmacokinetic profile of MS-275 in subjects with metastatic melanoma

Detailed Description
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The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer Schering Pharma AG, Germany.Bayer Schering Pharma AG, Germany is the sponsor of the trial.

Official Title
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Phase II Study of MS-275, a Histone Deacetylase Inhibitor, Comparing 2 Dosage Schedules in Patients With Metastatic Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Histone Deacetylase Inhibitor, MS-275 (BAY 86-5274, ZK 244894)
* Drug: Histone Deacetylase Inhibitor, MS-275 (BAY 86-5274, ZK 244894)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects with Stage III or IV non-resectable nonuveal (cutaneous or mucosal) metastatic melanoma who had received at least one but no more than two previous systemic therapies (immunotherapy and/or chemotherapy) for metastatic disease and who had not responded to or who had progressed after their most recent therapy were eligible for enrollment Presence of at least one lesion fulfilling the minimum Response Evaluation Criteria in Solid Tumors (RECIST) size requirements for a target lesion - Use of highly effective birth control methods in females of child-bearing potential Able to undergo either contrast enhanced computed tomography (CT) scan or contrast enhanced magnetic resonance imaging (MRI) scan for tumor assessment Life expectancy greater than 3 months Adequate organ and bone marrow functions as defined below: absolute neutrophil count ≥ 1500 /µL, platelets ≥ 100,000 /µL, creatinine ≤ 1.5 × upper limit of normal (ULN) or measured creatinine clearance of ≥ 60 mL/min x 1.73 m2 body surface area, total bilirubin ≤ 1.5 times ULN, aspartate aminotransferase or serum glutamic oxalacetic transaminase/alanine aminotransferase or serum glutamic pyruvic transaminase∗ ≤ 2.5 times ULN Negative serum pregnancy test within 2 weeks prior to receiving the first dose of study drug in female subjects of childbearing potential. Agreement to use a highly effective method of birth control throughout the study period and 3 months thereafter for sexually active males and females of childbearing potentia Exclusion Criteria: Active malignancy in the last five years Pregnancy, breast feeding HIV infection Brain metastasis Concomitant use of corticosteroids or valproic acid Uncontrolled intercurrent illness Diagnosis of uveal melanoma Eastern Cooperative Oncology Group performance status ≥ 2 Ongoing effects from previous investigational drug studies or concomitant participation in other investigational drug studies Prior use of MS-275 or any other HDAC inhibitor History of allergic reactions attributed to compounds of similar chemical or biologic composition to MS-275 Anticancer therapy Active gastrointestinal conditions that might predispose for poor drug absorption Major surgery within 4 weeks prior to enrollment Hypophosphatemia < 2.5 mg/dL at screening, if not corrected in the screening period Medical, psychiatric or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Histone Deacetylase Inhibitor, 3 mg<br>Subjects received 3 mg MS-275 orally biweekly (Days 1 and 15 of a 4 week cycle) or until disease progression or unacceptable toxicity | Drug: Histone Deacetylase Inhibitor, MS-275 (BAY 86-5274, ZK 244894)<br>* MS-275, 3 mg on Days 1 and 15 of a 4-week cycle<br>|
| Experimental: Histone Deacetylase Inhibitor, 7 mg<br>Subjects received 7 mg MS-275 orally weekly (Days 1, 8, and 15 of a 4 week cycle) until disease progression or unacceptable toxicity | Drug: Histone Deacetylase Inhibitor, MS-275 (BAY 86-5274, ZK 244894)<br>* MS-275, 7 mg on Days 1, 8 and 15 of a 4-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall tumor response rate (the proportion of subjects with the best tumor response of PR or CR within the first 6 cycles of treatment) |  | Baseline, 8, 16, 24, 32 weeks (cycle 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression |  | Baseline, every 8 weeks until progression | 
| Survival |  | At 6 months | 
| Tumor response rate at each tumor assessment time point (CR/PR/SD/PD/not assessable) |  | At baseline and repeated every 2 cycles until tumor progression between Day 22 of even numbered cycles and Day 1 of subsequent odd numbered cycle and also at EOT and F-up visiit (90 days after the EOT and every 3 months until disease progression) | 
| Time to death |  | Baseline, every 8 weeks until death | 
| Number of participants with adverse events |  | Approximately 8-64 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-resectable metastatic melanoma