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

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Primary Outcome Measures

Name	Time	Method
to evaluate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT)	throughout the study

Secondary Outcome Measures

Name	Time	Method
to assess the pharmacodynamics and pharmacokinetics of CRO11-vcMMAE	throughout the study
to evaluate the immune response to CR011-vcMMAE	throughout the study
to explore clinical anti-tumor response of CR011-vcMMAE in subjects with advanced metastatic melanoma	throughout the study

Locations (4): New York University Medical Center
🇺🇸
New York, New York, United States
Angeles Clinic and Research Institute
🇺🇸
Santa Monica, California, United States
M.D. Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Yale University
🇺🇸
New Haven, Connecticut, United States