Conditions: Metastatic Melanoma Skin Cancer Neoplasm
Keywords: metastatic melanoma ADI ADI-PEG 20 ADI SS PEG 20,000mw arginine enzyme therapy
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 31
Healthy volunteers: no

Brief summary:
This was a phase 1/2, open-label, dose-escalation study of arginine deiminase linked via succinimidyl succinate to polyethylene glycol of 20,000 molecular weight (ADI-PEG 20) in subjects with advanced melanoma. ADI-PEG 20 was administered intramuscularly (IM) at escalating doses weekly for 9 weeks (cycle 1) or 8 weeks (subsequent cycles). The primary objectives were to the establish the safety, tolerability, and clinical efficacy of ADI-PEG 20. Secondary objectives included evaluation of the metabolic activity by \[18F\]-fluorodeoxyglucose positron emission tomography (FDG PET), pharmacodynamics, correlation of immunogenicity with clinical response, and correlation of argininosuccinate synthetase (ASS) tumor expression with clinical response.

Detailed description:
A 3+3 design was implemented during phase 1, in which 3 to 6 subjects were enrolled sequentially into the following escalating dose cohorts:

* Cohort 1 (40 IU/m\^2)
* Cohort 2 (80 IU/m\^2)
* Cohort 3 (160 IU/m\^2)

Subjects were monitored for dose-limiting toxicity (DLT) during the first 2 weeks of cycle 1, with DLT defined as any grade 3 or higher toxicity. The maximum tolerated dose (MTD) was defined as the cohort in which \< 33% of subjects (ie, 0/3 or 1/6 subjects in a cohort) experienced DLT. In phase 2, the MTD cohort was expanded in up to 25 patients.

Subjects who completed treatment in cycle 1 without DLT were eligible to initiate cycle 2 at week 10 provided that a computed tomography (CT) scan showed either enlargement of existing disease without accompanying symptoms OR stable disease or improvement with no unacceptable toxicity. The same radiologic criteria applied for initiation of subsequent cycles. Subjects could continue to receive study treatment until disease progression.

Arms:
arm 1: Subjects received ADI-PEG 20 at a dose of 40 IU/m\^2 arm 2: Subjects received ADI-PEG 20 at a dose of 80 IU/m\^2 arm 3: Subjects received ADI-PEG 20 at a dose of 160 IU/m\^2

Interventions: intervention 1: ADI PEG 20
Intervention descriptions: intervention 1: Intramuscular injections were administered into the deltoid, gluteal, or quadricep muscles once weekly (± 2 days) for 9 weeks during cycle 1 and 8 weeks during subsequent cycles

Protocol document: