Phase II Evaluation of Concurrent Ipilimumab Therapy and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Malignant Melanoma
1. To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma
based on 1-year and 2-year overall survival.
2. To evaluate the safety and tolerability of concurrent ipilimumab therapy and SART of
melanoma based on CTCAE grading of toxicities, and to identify any novel or unexpected
Grade 3 or 4 toxicities thought specifically related to ipilimumab and concurrent SART
during first 3 cycles of ipilimumab therapy (prior to week 9) in a Phase II study.
1. To evaluate the 1-year and 2-year disease control rates (CR+PR+SD)
2. Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO
3. Characterize overall survival by Kaplan-Meier analysis.
1. Evaluate individual lesion control (<25% progression) following body SART at 6, 12, 24
2. Describe number of patients requiring retreatment of any local lesion with surgery or
3. Describe the incidence of new brain metastases following ipilimumab therapy.
4. Describe the incidence of treatment related toxicity and/or symptomatic bleeding,
perforation, or necrosis at SART treated tumor sites.
5. Explore the use of circulating melanoma cells and serum metastasis gene expression
levels as prognostic and predictive (intermediate) markers to identify responding
6. Assess the effect of therapy on quality of life, using ECOG score as a surrogate.
Ipilimumab may markedly enhance the immunologic responses to tumor antigen released from
necrotic tumor cells by radiotherapy by promoting cytotoxic T cell activation, while
preventing induction of antigen tolerance. In addition, further beneficial immunologic
effects may be achieved by the reduction in the amount of viable tumor cell mass. The net
effect may be to promote a significantly enhanced antitumor T cell response. This will
result in improved 1-year and 2-year survival, especially if a minimal or microscopic
disease state can be achieved within a patient following SART.
Biologic Correlation Studies:
There are currently no standard prognostic or predictive markers to evaluate or predict
outcome of ipilimumab therapy. This study provides the opportunity for exploratory analysis
of several candidate hypotheses that may predict outcome.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity
Wolfram Samlowski, MD
Comprehensive Cancer Centers of Nevada
United States: Institutional Review Board
|Comprehensive Cancer Centers of Nevada||Las Vegas, Nevada 89109|