RAMPART : a phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse
Abstract
Background 20–60% of patients with initially locally advanced Renal Cell Carcinoma (RCC) develop metastatic disease despite optimal surgical excision. Adjuvant strategies have been tested in RCC including cytokines, radiotherapy, hormones and oral tyrosine-kinase inhibitors (TKIs), with limited success. The predominant global standard-of-care after nephrectomy remains active monitoring. Immune checkpoint inhibitors (ICIs) are effective in the treatment of metastatic RCC; RAMPART will investigate these agents in the adjuvant setting. Methods/design RAMPART is an international, UK-led trial investigating the addition of ICIs after nephrectomy in patients with resected locally advanced RCC. RAMPART is a multi-arm multi-stage (MAMS) platform trial, upon which additional research questions may be addressed over time. The target population is patients with histologically proven resected locally advanced RCC (clear cell and non-clear cell histological subtypes), with no residual macroscopic disease, who are at high or intermediate risk of relapse (Leibovich score 3–11). Patients with fully resected synchronous ipsilateral adrenal metastases are included. Participants are randomly assigned (3,2:2) to Arm A - active monitoring (no placebo) for one year, Arm B - durvalumab (PD-L1 inhibitor) 4-weekly for one year; or Arm C - combination therapy with durvalumab 4-weekly for one year plus two doses of tremelimumab (CTLA-4 inhibitor) at day 1 of the first two 4-weekly cycles. The co-primary outcomes are disease-free-survival (DFS) and overall survival (OS). Secondary outcomes include safety, metastasis-free survival, RCC specific survival, quality of life, and patient and clinician preferences. Tumour tissue, plasma and urine are collected for molecular analysis (TransRAMPART).
Citation
Oza , B , Frangou , E , Smith , B , Bryant , H , Kaplan , R , Choodari-Oskooei , B , Powles , T , Stewart , G D , Albiges , L , Bex , A , Choueiri , T K , Davis , I D , Eisen , T , Fielding , A , Harrison , D , McWhirter , A , Mulhere , S , Nathan , P , Rini , B , Ritchie , A , Scovell , S , Shakeshaft , C , Stockler , M R , Thorogood , N , Parmar , M K B , Larkin , J & Meade , A 2021 , ' RAMPART : a phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse ' , Contemporary Clinical Trials , vol. 108 , 106482 . https://doi.org/10.1016/j.cct.2021.106482
Publication
Contemporary Clinical Trials
Status
Peer reviewed
ISSN
1551-7144Type
Journal article
Description
AstraZeneca LP have provided an educational grant for the trial and free of charge durvalumab and tremelimumab. A small grant is also provided by Kidney Cancer UK. MRC CTU at UCL also provides funding for staff working on the trial. The TransRAMPART sample collection is being funded by a Prospective Sample Collection award from Cancer Research UK.Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.