A Phase I/II Study of CR011-vcMMAE in Subjects With Unresectable Stage III or Stage IV Melanoma

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability and pharmacokinetics of CR011-vcMMAE in patients who have unresectable stage III or stage IV melanoma and have failed no more than 1 line of prior cytotoxic therapy. CR011-vcMMAE will be administered intravenously (IV) once every 3 weeks at escalating doses until the maximum tolerated dose (MTD) is reached. Once the MTD is defined, 18-32 patients will be enrolled to further evaluate the safety and efficacy of CR011-vcMMAE at this dose level. Additional dosing schedules of CR011-vcMMAE will also be explored.

Official Title
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A Phase I/II Study of CR011-vcMMAE in Subjects With Unresectable Stage III or Stage IV Melanoma

Conditions
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Unresectable Stage III or Stage IV Melanoma

Intervention / Treatment
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* Drug: CR011-vcMMAE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female with age ≥ 18 years. Progressive or new metastatic melanoma, stage III or IV. Measurable disease by CT / MRI Failure of no more than 1 line of prior cytotoxic therapy. Adequate bone marrow, renal and hepatic function Leukocytes ≥ 3000/mm3, ANC ≥ 1,500 cells/mm3, Platelets ≥ 100,000/mm3 Hemoglobin ≥ 10 g/dL (transfusion allowed) Total bilirubin ≤ 1.5 x upper normal limit (UNL) AST (SGOT), ALT (SGPT) ≤ 3.0 x UNL (≤ 5.0 x UNL may be acceptable) Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance > 45 mL/min/1.73 m2 PT/aPTT < 1.5 x UNL or within therapeutic range via anti-coagulation therapy Karnofsky PS ≥ 70%. Estimated life expectancy > 3 months. Signed informed consent approved IRB and ability to comply with the study or monitoring procedures. Subjects with evaluable disease are eligible in dose-escalation cohorts Exclusion Criteria: Prior therapies for disease under study less than 4 weeks prior to enrollment. Major surgery or trauma within 4 weeks of enrollment. Active brain metastases Active chronic inflammatory, autoimmunity, immunodeficiency disease, and vascular or hemorrhagic disorders. History of allergic reactions to dolastatin, auristatin or compounds of similar composition. Significant cardiovascular disease Other malignancies Pregnancy or breast feeding Refusal or inability to use effective means of contraception (for men, and women with childbearing potential) History of or test-positive to HIV, or hepatitis B or C

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: CR011-vcMMAE|administered as an intravenous infusion of 250 mL over 90 min|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) |  | throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the immune response to CR011-vcMMAE |  | throughout the study | 
| to assess the pharmacodynamics and pharmacokinetics of CRO11-vcMMAE |  | throughout the study | 
| to explore clinical anti-tumor response of CR011-vcMMAE in subjects with advanced metastatic melanoma |  | throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, CR011-vcMMAE