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

Bhavna Oza, Eleni Frangou, Ben Smith, Hanna Bryant, Rick Kaplan, Babak Choodari-Oskooei, Tom Powles, Grant D. Stewart, Laurence Albiges, Axel Bex, Toni K. Choueiri, Ian D. Davis, Tim Eisen, Alison Fielding, David Harrison, Anita McWhirter, Salena Mulhere, Paul Nathan, Brian Rini, Alastair RitchieSarah Scovell, Clare Shakeshaft, Martin R. Stockler, Nat Thorogood, Mahesh K.B. Parmar, James Larkin, Angela Meade

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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). Trial registration: ISRCTN #: ISRCTN53348826, NCT #: NCT03288532, EUDRACT #: 2017–002329-39, CTA #: 20363/0380/001–0001, MREC #: 17/LO/1875, ClinicalTrials.gov Identifier: NCT03288532, RAMPART grant number: MC_UU_12023/25, TransRAMPART grant number: A28690 Cancer Research UK, RAMPART Protocol version 5.0.

Original languageEnglish
Article number106482
JournalContemporary Clinical Trials
Volume108
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • Check-point inhibitor
  • Durvalumab
  • MAMS
  • Platform trial
  • RAMPART
  • Renal cancer
  • Tremelimumab

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