Study of MDX-010 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
This is a Phase I, open-label, multicenter, pharmacokinetic study of MDX-010 in up to 90 evaluable subjects with surgically unresectable malignant melanoma.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label Pharmacokinetic and Safety Study of MDX-010 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma|
- To determine the safety and pharmacokinetic profile of single and multiple doses of MDX-010. [ Time Frame: up to approximately 1 year ] [ Designated as safety issue: Yes ]
- Determine the clinical activity profile of single and multiple doses of MDX-010 [ Time Frame: up to aproximately one year. ] [ Designated as safety issue: No ]
|Study Start Date:||July 2003|
|Study Completion Date:||June 2007|
|Primary Completion Date:||October 2005 (Final data collection date for primary outcome measure)|
Group A: Six to 12 subjects will be treated with transfectoma-derived MDX-010 at 2.8 or 5 mg/kg/dose, or with hybridoma-derived MDX-010 at 3 mg/kg/dose administered on Days 1, 57, and 85. The 2.8, 3, and 5 mg/kg dosage cohorts may be initiated concurrently. Additionally, 6 subjects per cohort will receive single doses of transfectoma-derived MDX-010 at 7.5, 10, 15, and 20 mg/kg.
Dose escalation from the 5 mg/kg cohort to the 7.5 mg/kg cohort will depend on the safety profile following a single dose of 5 mg/kg. Once all subjects are enrolled in the 5 mg/kg cohort and 4 weeks have elapsed since the sixth subject in the cohort has received the first infusion, dose escalation to the 7.5 mg/kg cohort may occur if ≤1 DLT has occurred in the 5 mg/kg cohort. Dose escalation to the 10 mg/kg cohort may occur 4 weeks after the sixth subject in the 7.5 mg/kg/dose cohort has received the first infusion (with ≤1 DLT). Dose escalation to the 15 and 20 mg/kg cohorts may occur 4 weeks after the sixth subject in the previous cohort has received the first infusion (with ≤1 DLT). Up to six additional subjects may be enrolled in the MTD dose cohort or in the 20 mg/kg dose cohort if MTD is not attained.
Group B: If single-dose administration of MDX-010 at 10 mg/kg is well tolerated (≤1 DLT in the cohort in Group A), then an additional 12 to 20 subjects will be enrolled and treated with MDX-010 at 10 mg/kg/dose administered on Days 1, 22, 43, and 64.
Subjects who respond to therapy will be followed until disease progression or a maximum of approximately 1 year. Subjects with a response of SD ≥ 3 months, PR, or CR to their initial treatment cycle who subsequently relapse may be eligible for retreatment with the same regimen or an alternate regimen considered to be more effective at the time of retreatment.
|United States, Arizona|
|Arizona Cancer Center|
|Tucson, Arizona, United States, 85724-5024|
|United States, California|
|USC/Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, North Carolina|
|Piedmont Oncology Specialists|
|Charlotte, North Carolina, United States, 28207|
|United States, Oregon|
|Providence Portland Medical Center|
|Portland, Oregon, United States, 97213|
|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|