Systemic Therapy With Interferon, Interleukin-2 and BRAF Inhibitor
The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of vemurafenib and Aldesleukin (interleukin-2) that can be given in combination with interferon alfa-2b in patients with advanced or metastatic melanoma. The safety of this combination will also be studied.
The goal of Phase II is to learn if this study drug combination can help to control advanced or metastatic melanoma.
Vemurafenib is designed to interact with cancer cells at the site of BRAF mutation. This may cause the cancer cells to die.
Interferon alfa-2b and aldesleukin are designed to increase the ability of immune system cells to fight cancer cells.
Drug: Interferon Alpha-2b
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Systemic Therapy of Metastatic Melanoma With Multidrug Regimen Including Interferon, Interleukin-2 and BRAF Inhibitor|
- Maximum Tolerated Dose (MTD) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]Maximum tolerated dose (MTD) defined as highest dose studied in which incidence of dose limiting toxicity (DLT) was less than 33%. DLT defined as any grade 3 or 4 non-hematological toxicity excluding manageable N/V, diarrhea and fatigue and manageable/replaceable grade 3 or 4 electrolyte abnormalities, and appearance of new squamous cell skin cancers. Toxicity that may result in delaying next course for more than 3 weeks. Any grade 4 neutropenia more than 7 days duration or Grade 4 thrombocytopenia lasting more than 7 days.
- Progression-Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]Progression-free survival estimated using the method of Kaplan-Meier. It will be determined from the start of the study until disease progression or death, whichever is first.
|Study Start Date:||March 2013|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Experimental: Vemurafenib + IL-2 + Interferon Alfa-2b
Starting dose of Vemurafenib 720 mg by mouth twice daily. Three dose levels of Vemurafenib evaluated in combination with interferon and IL-2. These doses are 480 mg, 720 mg and 960 mg. IL-2 given by continuous venous infusion at starting IL-2 dose of 7 million IU/m2 daily for 4 days (total of 96 hours, days 2-5) starting day 2. IL-2 dose levels are 5MU/m2/day, 7MU/m2/day and 9MU/m2 day. Doses of interferon remain constant at 5 MU/m2 subcutaneously daily for 5 days starting Day 1.
Phase I Starting dose: 720 mg by mouth twice a day for a 21 day cycle.
Phase II Starting dose: Maximum tolerated dose (MTD) from Phase I.
Other Names:Drug: IL-2
Phase I Starting Dose: 7 million IU/m2 by vein on Days 2 - 5 of a 21 day cycle.
Phase II Starting Dose: Maximum tolerated dose (MTD) from Phase I.
Other Names:Drug: Interferon Alpha-2b
5 million U/m2 subcutaneously on Days 1 - 5 of a 21 day cycle.
Other Name: Intron A
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