A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol.

ABSTRACT

BACKGROUND: The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction with immunotherapy may provide more durable control and pre-clinical models have suggested a synergistic immune-priming effect of SABR. OBJECTIVES: and Methods: RAPPORT is a prospective, single arm, phase I/II study assessing the safety, efficacy and biological effects of single fraction SABR followed by pembrolizumab for oligometastatic ccRCC. The study will include 30 patients with histological confirmed ccRCC and 1-5 oligometastases, one or more of which must be suitable for SABR. Patients can have received prior systemic therapy but not prior immunotherapy. A single 20Gy of SABR is followed 5 days later by 8 cycles of 200 mg pembrolizumab, every 3 weeks. Adverse events are recorded using CTCAE V4.03 and tumour response evaluated by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Tumour tissue and peripheral blood samples will be collected pre-, during and post-treatment to assess longitudinal changes in immune subsets. OUTCOMES AND SIGNIFICANCE: The RAPPORT study will provide important safety and early efficacy data on the combination of SABR and pembrolizumab in oligometastatic ccRCC and will provide an insight into the underlying biological effects of combination therapy. TRIAL REGISTRATION clinicaltrials.gov ID NCT02855203.