This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated).
The study is planned based on a two-stage design that allows early termination for lack of efficacy. A safety run-in phase will be included comprising the first 6 patients at minimum to ensure that the combination of nivolumab plus ipilimumab and SBRT is safe. Then, the investigators will determine whether the combination of nivolumab plus ipilimumab and SBRT yields a clinically compelling antitumor activity measured as objective response rate (ORR), and evaluate other endpoints including Thrombotic thrombocytopenic purpura (TTP), duration of response (DOR), progression free survival (PFS), overall survival (OS) and local control of irradiated sites. There is no previous experience with SBRT used concurrently with nivolumab and ipilimumab in this study population. Therefore, to ensure that the combination is safe, the first six patients will be treated and observed for toxicity for 6 weeks after radiation before continuing with further accrual. Therefore, six patients will be enrolled at the proposed dose of nivolumab and ipilimumab in combination with SBRT. If 4 out of the first 6 patients experience Grade 3/4 toxicity or a lower grade toxicity requiring immune suppressive therapy during the safety run-in observation period (defined as the first 4-cycles, 12 weeks), enrollment will cease and the study will be halted until further safety analysis of the combination regimen can be performed. If less than 4 out of the first 6 patients experience Grade 3/4 toxicities or require steroids, the investigators will proceed with additional accrual with this regimen.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
IV immunotherapy
SBRT will be delivered in conjunction with immunotherapy
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
UT Southwestern
Dallas, Texas, United States
Number of Participants With Treatment-related Adverse Events Grade 3 or Higher as Assessed by CTCAE v4.0
An adverse event (AE) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: up to 35 months
Number of Participants Needing Corticosteroids
Time frame: up to 35 months
Objective Response Rate (ORR)
The ORR is defined as the number of participants with a BOR of CR (Complete response) or PR (Partial response) divided by the number of treated participants. The BOR (Best overall response) is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy including radiotherapy, tumor-directed surgery, or systemic anticancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment
Time frame: up to 35 months
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