Stereotactic Body Radiation Therapy and Ipilimumab in Treating Patients With Stage IV Melanoma
This phase II trial studies the side effects of stereotactic body irradiation (SBRT) and to see how well it works when given together with ipilimumab in treating patients with stage IV melanoma. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving SBRT with ipilimumab may be effective in treating melanoma.
Stage IV Melanoma
Radiation: stereotactic body radiation therapy
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||RADVAX: A Stratified Phase II Dose Escalation Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Metastatic Melanoma|
- Late toxicities, graded according to the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and the Treatment of Cancer (EORTC) late morbidity scoring system [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]Defined generally as an adverse event associated with the treatment which occurs beyond 30 days after last injection (i.e., adverse events which are observed months after treatment are most likely associated with SBRT). All dose-limiting toxicities and late toxicities will be graded and tabled by lesion site stratum and SBRT fraction dose level. Toxicity attribution to either SBRT or ipilimumab will be described if possible.
- Immune-related clinical response, defined as proportion of patients treated at the MTD who achieve either a complete or partial immune-related response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]The number of immune-related responses will be tabled by stratum and SBRT fraction dose level. At the MTD, the immune-related response rate and 95% exact confidence interval (CI) will be estimated separately for previously untreated and previously treated metastatic patients.
- Immune-related progression-free survival [ Time Frame: Time from first day of radiotherapy to first documented immune-related progressive disease, death due to any cause or last patient contact alive and progression-free, assessed at 6 months ] [ Designated as safety issue: No ]Will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.
- Overall survival [ Time Frame: Time from first day of radiotherapy to death due to any cause or last patient contact alive, assessed at 12 months ] [ Designated as safety issue: No ]Will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.
- Lymphocyte analysis and activation [ Time Frame: Up to 30 days after last ipilimumab injection ] [ Designated as safety issue: No ]Outcomes will first be described using plots and descriptive statistics. Natural log transformation may be applied, as necessary, prior to statistical comparison. Within-patient differences (e.g., baseline vs. post-treatment) will be examined by Student's t test for paired data or nonparametric Wilcoxon signed ranks test.
- T cell response [ Time Frame: Up to 30 days after last ipilimumab injection ] [ Designated as safety issue: No ]The number of immune responses (> 2 fold pre/post increase) will be tabled by fraction dose level. The overall immune response rate and 95% exact CI will be estimated separately for previously untreated and previously treated metastatic patients treated at the MTD.
|Study Start Date:||March 2014|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (SBRT, ipilimumab)
Patients undergo a total of 3 fractions of SBRT between days 1-13. Patients then receive ipilimumab IV every 3 weeks. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Radiation: stereotactic body radiation therapy
Other Names:Biological: ipilimumab
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To determine, for each stratum, immune-related clinical response rate, immune-related progression-free survival rate at 6 months (irPFS6), and overall survival rate at 12 months (OS12).
I. To gather additional data on acute and late toxicity and immune pharmacodynamic changes.
OUTLINE: Patients undergo a total of 3 fractions of SBRT between days 1-13. Patients then receive ipilimumab intravenously (IV) every 3 weeks. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, within 60 days, and then every 3 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01970527
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Ramesh Rengan 206-598-4110|
|Principal Investigator: Ramesh Rengan|
|Principal Investigator:||Ramesh Rengan||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|