Spots Global Cancer Trial Database for Evaluating the Combination of MK-3475 and Sterotactic Body Radiotherapy in Patients With Metastatic Melanoma or NSCLC

Study Description

Brief Summary: This is a 2-part prospective trial examining the ability of Stereotactic Body Radiation Therapy (SBRT) to induce a response to MK-3475, a humanized antibody to PD-1, in patients who progress on this antibody. Patients with metastatic melanoma will be enrolled after they have progressed on anti-PD-1 therapy. Patients with metastatic NSCLC (previously untreated with anti-PD-1 or anti-PD-L1 therapy) will be enrolled and treated with MK-3475 until they exhibit progression of disease. At this point (when patients have demonstrated progression of disease) a single target lesion will be selected and treated with SBRT, and then MK-3475 will be restarted and continued until there is further progression of disease. The first phase of the study is a radiation dose escalation with a constant dose of MK-3475. The second part of the study includes expansion cohorts of NSCLC and melanoma patients.

Detailed Description: The phase 1b portion of the trial is a radiation dose escalation study to determine the maximum tolerated dose (MTD) of SBRT when given to patients previously and subsequently exposed to MK-3475. Because the class of PD-1 inhibitory antibodies conveys a risk of pneumonitis, there will be two parallel dose escalation arms- Arm A will include SBRT targets in the lung parenchyma, and Arm B will be limited to targets outside the lung parenchyma. Each arm will be separately escalated, and two MTDs will be determined. The starting dose will be 3000 cGy in 5 fractions; there will be one dose escalation cohort (3000 cGy in 3 fractions), and if necessary one dose de-escalation cohort (1000 cGy in a single fraction). If there is dose-limiting toxicity at the lowest cohort, that arm will be closed and SBRT to that site will be discontinued. The phase 2a portion of the study includes 2 expansion cohorts, for melanoma and NSCLC, with SBRT delivered at the MTD. The primary endpoint of this phase of the study is the overall response rate to post-SBRT MK-3475. Secondary endpoints include determining the time to progression, overall survival, and exploratory biomarkers. IND exempt per FDA. Inclusion/Exclusion Criteria Updated 4/7/2016

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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