Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma (SART)
The purpose of this study is to evaluate if precisely-targeted radiation therapy, known as stereotactic ablative radiotherapy (SART), given during treatment with the drug ipilimumab (Yervoy) will improve survival for patients with melanoma that has spread to five or fewer sites (oligometastatic).
Blood samples will be collected for research purposes. Planned studies include exploration of certain gene mutations and serum markers as predictors of response to ipilimumab treatment. Research lab studies will also evaluate if circulating tumor cells (CTC) can be accurately detected and isolated from the blood using novel laboratory techniques and if they are a prognostic/predictive marker for treatment response. Test results will not be given to participants or their physicians. In some cases, CTC may be grown for long-term cell lines for further research.
|Melanoma||Drug: Ipilimumab Radiation: Stereotactic Ablative Radiosurgery (SART)||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Evaluation of Concurrent Ipilimumab Therapy and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Malignant Melanoma|
- Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity [ Time Frame: Week 9 ]
- Safety and tolerability of concurrent ipilimumab and SART - Subacute Toxicity [ Time Frame: Week 15 ]
- 1-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria [ Time Frame: 2 year minimum follow up on study participants ]
- 2-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria [ Time Frame: 2 year minimum follow up on study participants ]
- 1-year overall survival [ Time Frame: 2 year minimum follow up on study participants ]
- 2-year overall survival [ Time Frame: 2 year minimum follow up on study participants ]
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Experimental: Ipilimumab + SART
Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab.
Ipilimumab 10mg/kg administered intravenously over 90-minute period every 3 weeks for a total of four doses as tolerated. Maintenance ipilimumab (10 mg/kg intravenously every 3 months) will be administered beginning Week 24, as long as there is clinical benefit in the opinion of the investigator using immune related response criteria, and there are no novel or unexpected Grade 3 or 4 toxicities.
Other Names:Radiation: Stereotactic Ablative Radiosurgery (SART)
Definitive radiotherapy will be administered to up to 1-5 lesions using SART techniques after initial dose of ipilimumab. Radiotherapy will be timed before start of 3rd cycle of ipilimumab treatment to maximize synergy (week 6).
- To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma based on 1-year and 2-year overall survival.
- 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.
- To evaluate the 1-year and 2-year disease control rates (CR+PR+SD)
- Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO criteria.
- Characterize overall survival by Kaplan-Meier analysis.
- Evaluate individual lesion control (<25% progression) following body SART at 6, 12, 24 months.
- Describe number of patients requiring retreatment of any local lesion with surgery or other treatments.
- Describe the incidence of new brain metastases following ipilimumab therapy.
- Describe the incidence of treatment related toxicity and/or symptomatic bleeding, perforation, or necrosis at SART treated tumor sites.
- Explore the use of circulating melanoma cells and serum metastasis gene expression levels as prognostic and predictive (intermediate) markers to identify responding patients.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01565837
|Contact: Wolfram Samlowski, MDemail@example.com|
|Contact: Khin Winfirstname.lastname@example.org|
|United States, Nevada|
|Comprehensive Cancer Centers of Nevada||Recruiting|
|Las Vegas, Nevada, United States, 89148|
|Contact: Khin Win 702-419-5550 email@example.com|
|Principal Investigator:||Wolfram Samlowski, MD||Comprehensive Cancer Centers of Nevada|