Clinical trial NCT00679289
Conditions: Metastatic Melanoma Cutaneous Melanoma
Keywords: KW2871 Ecromeximab Anti-ganglioside Antibody Interferon alpha Metastatic melanoma
Sponsor: Ludwig Institute for Cancer Research
Start date: 2008-03-28; Completion date: 2014-02-03
Enrollment: 36 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a Phase 2, open-label study of KW2871 (ecromeximab) in combination with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. The primary objectives of this study were to assess progression-free survival (PFS) and safety. The secondary objectives were to assess the objective response rate, KW2871 pharmacokinetics (PK), and other exploratory immunology as indicated (e.g., development of human anti-chimeric antibodies \[HACA\], activity of antibody-dependent cell-mediated cytotoxicity \[ADCC\] and complement-dependent cytotoxicity \[CDC\] in peripheral blood, number and functional state of tumor-infiltrating immune cells and expression of GD3 in immune and tumor cells of tumor biopsies, and markers of interferon \[IFN\] response/resistance and markers of resistance to ADCC/CDC in peripheral blood mononuclear cells \[PBMCs\]).

Detailed description:
Eligible patients were sequentially enrolled into dose-escalating cohorts to receive KW2871 intravenously (IV) once every 2 weeks starting on Day 3 of Week 1 at the following doses: 5 mg/m\^2 in Cohort 1, 10 mg/m\^2 in Cohort 2, and 20 mg/m\^2 in Cohort 3. HDI was administered concurrently at a dose of 20 million units (MU)/m\^2 IV once daily (QD) for 5 consecutive days per week for 4 weeks (induction phase), followed by 10 MU/m\^2 administered subcutaneously (SC) 3 times per week (maintenance phase). Patients received KW2871 and HDI combination therapy until disease progression requiring treatment intervention that would have interfered with the interpretation of the study results.

Initially, 3 patients were enrolled within a cohort and evaluated for dose-limiting toxicity (DLT) and regimen-limiting toxicity (RLT) for the first 8 weeks of study treatment. If 1 of 3 patients experienced an RLT, the cohort was expanded to 6 patients. Escalation to the next higher dose cohort proceeded if the RLT rate was \<33% (0/3 or 1/6 patients) in a given cohort. The combination treatment was considered safe if ≤ 20% patients experienced RLT.

DLT was defined as any adverse event (AE) that required reduction of the HDI dose or discontinuation of KW2871. RLT was defined as an HDI-related DLT that required more than 2 dose reductions of HDI during the induction phase or the first 4 weeks of the maintenance phase, or any KW2871- or regimen-related DLT.

Arms: arm 1: KW2871: 5 mg/m\^2 IV every 2 weeks until disease progression

HDI: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week until disease progression arm 2: KW2871: 10 mg/m\^2 IV every 2 weeks until disease progression

HDI: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week until disease progression arm 3: KW2871: 20 mg/m\^2 IV every 2 weeks until disease progression

HDI: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week until disease progression
Interventions: intervention 1: HDI intervention 2: KW2871 intervention 3: KW2871 intervention 4: KW2871
Intervention descriptions: intervention 1: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week until disease progression intervention 2: 5 mg/m\^2 IV every 2 weeks until disease progression intervention 3: 10 mg/m\^2 IV every 2 weeks until disease progression intervention 4: 20 mg/m\^2 IV every 2 weeks until disease progression

Protocol documents: