Clinical trial NCT00412828: A Phase I/II Study of CR011-vcMMAE in Subjects With Unresectable Stage III or Stage IV Melanoma
Official title: A Phase I/II Study of CR011-vcMMAE in Subjects With Unresectable Stage III or Stage IV Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Unresectable Stage III or Stage IV Melanoma
Keywords: Melanoma
CR011-vcMMAE
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-12-19
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: to evaluate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT)
timeFrame: throughout the study
Secondary outcomes:
measure: to evaluate the immune response to CR011-vcMMAE
timeFrame: throughout the study
measure: to assess the pharmacodynamics and pharmacokinetics of CRO11-vcMMAE
timeFrame: throughout the study
measure: to explore clinical anti-tumor response of CR011-vcMMAE in subjects with advanced metastatic melanoma
timeFrame: throughout the study
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Angeles Clinic and Research Institute
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
Study officials:
References:
citation: Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, Simantov R, Crowley E, Green JA, Hawthorne T, Davis TA, Sznol M, Hwu P. Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with advanced melanoma. J Clin Oncol. 2014 Nov 10;32(32):3659-66. doi: 10.1200/JCO.2013.54.8115. Epub 2014 Sep 29.