Conditions: Melanoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 22
Healthy volunteers: no

Brief summary:
To determine the safety of local palliative radiation therapy used in combination with anti-CTLA-4 immunotherapy.

Detailed description:
This is a single institution, open-label, pilot study of palliative radiation therapy (RT) combined with ipilimumab in patients with stage IV melanoma. The primary objective of this study is to assess the safety of combining ipilimumab with palliative RT in patients with Stage IV melanoma. Secondary objectives are a) to assess the induction of anti-melanoma immune responses using laboratory correlative studies of T cell responses to melanoma antigens, and b) to compare tumor response rates and duration of response at unirradiated sites with responses in patients with Stage IV disease treated with ipilimumab alone on expanded access study CA184045. In this study, ipilimumab will be administered as recently approved by the FDA (3 mg/kg iv every 3 weeks for a total of 4 treatments). Palliative RT will start within 2 days of the first ipilimumab dose. Patients will be seen at least every 12 weeks for follow-up following completion of ipilimumab therapy until progression of disease by imaging criteria or increased symptomatology that requires another therapy. A total of 20 patients with previously treated unresectable metastatic melanoma requiring palliative radiation therapy will be treated on this pilot study over approximately 18 months. All subjects who receive study drug will be monitored for safety. Relevant tumor imaging studies will be obtained at baseline, 2-4 weeks following the 4th/last dose of ipilimumab, and then every 12 weeks until disease progression. This study will provide the safety data (and possibly early efficacy signals) needed to proceed with a randomized Phase II study for proof of principle. If compelling data is obtained supporting this IT + RT vaccine strategy, this approach will be extended to other solid tumor types.

Arms:
arm 1: Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1 to 2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2 to 4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease.

Interventions: intervention 1: Ipilimumab intervention 2: Radiation Therapy
Intervention descriptions: intervention 1: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. intervention 2: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.

Protocol document: