TY - JOUR
T1 - A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT)
T2 - Clinical trial protocol
AU - Pryor, David
AU - Bressel, Mathias
AU - Lawrentschuk, Nathan
AU - Tran, Ben
AU - Mooi, Jennifer
AU - Lewin, Jeremy
AU - Azad, Arun
AU - Colyer, Duncan
AU - Neha, Nitika
AU - Shaw, Mark
AU - Chander, Sarat
AU - Neeson, Paul
AU - Moon, Daniel
AU - Cuff, Katharine
AU - Wood, Simon
AU - Murphy, Declan G.
AU - Sandhu, Shahneen
AU - Loi, Sherene
AU - Siva, Shankar
N1 - Funding Information:
Funding support from Peter MacCallum Foundation philanthropic donation , drug supply by Merck Sharpe Dohme (MSD).
Publisher Copyright:
© 2021
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Immunotherapy
KW - Oligometastases
KW - RCC
KW - Renal cell carcinoma
KW - SABR
KW - SBRT
UR - http://www.scopus.com/inward/record.url?scp=85099259349&partnerID=8YFLogxK
U2 - 10.1016/j.conctc.2021.100703
DO - 10.1016/j.conctc.2021.100703
M3 - Article
C2 - 33490707
AN - SCOPUS:85099259349
SN - 2451-8654
VL - 21
JO - Contemporary Clinical Trials Communications
JF - Contemporary Clinical Trials Communications
M1 - 100703
ER -