Phase 1 Study of MPC-6827 and Temozolomide in Metastatic Melanoma

Study Overview
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Brief Summary
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This is an open-label, dose finding, multiple-dose study in subjects with metastatic melanoma. Three dose levels of MPC-6827 will be administered with temozolomide to three separate cohorts. Study endpoints will include determination of the maximum tolerated dose, determination of dose limiting toxicities, and evaluation of evidence of anti-tumor activity of MPC-6827 when given with temozolomide.

Official Title
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Dose Finding Phase 1 Study of the Treatment of Metastatic Melanoma With MPC-6827 in Combination With Temozolomide

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: MPC-6827 + Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven melanoma For subjects with brain metastases that require radiation, therapy must have been completed at least 4 weeks prior to Day 1 of Study Drug Have unresectable melanoma with measurable metastases Be a minimum of 4 weeks since prior surgical resection or major surgical procedure and a minimum of 2 weeks since chemotherapy/ biochemotherapy Performance score of Karnofsky ≥ 60%, or Eastern Cooperative Oncology Group (ECOG) ≤ 2, or WHO ≤ 2 If steroids are needed, be on a stable or decreasing dose of steroids for at least 1 week Exclusion Criteria: Hypersensitivity to Cremophor EL Have current/active intratumor hemorrhage by CT/MRI within 3 weeks prior to Day 1 of Study Drug confirmed by CT/MRI Have ocular melanoma Have primary intradural melanoma or leptomeningeal involvement Have cardiovascular disease (unstable angina or MI) Have cerebrovascular disease (stroke and/or TIA) Have uncontrolled hypertension Have a cardiac ejection fraction < 50% Have Troponin-I elevated above the normal range

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: MPC-6827 + Temozolomide|MPC-6827 at 2.1mg/m2, 2.7mg/m2 or 3.3mg/m2 administered by intravenous infusion over 2 hours once weekly for three weeks in a 4 week cycle. Temozolomide at 85 mg/m2 administered orally daily for 21 days in a 4 week cycle.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability; Maximum Tolerated Dose |  | After each cohort is enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  | Cycle 1 | 
| Antitumor Activity |  | Screening, end of each cycle, end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Metastatic