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.
Date
2021-09-16ICR Author
Author
Oza, B
Frangou, E
Smith, B
Bryant, H
Kaplan, R
Choodari-Oskooei, B
Powles, T
Stewart, GD
Albiges, L
Bex, A
Choueiri, TK
Davis, ID
Eisen, T
Fielding, A
Harrison, D
McWhirter, A
Mulhere, S
Nathan, P
Rini, B
Ritchie, A
Scovell, S
Shakeshaft, C
Stockler, MR
Thorogood, N
Parmar, MKB
Larkin, J
Meade, A
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Check-point inhibitor
Durvalumab
MAMS
Platform trial
RAMPART
Renal cancer
Tremelimumab
Carcinoma, Renal Cell
Chronic Disease
Humans
Kidney Neoplasms
Quality of Life
Recurrence
Language
eng
Date accepted
2021-06-09
License start date
2021-09-16
Citation
Contemporary Clinical Trials, 2021, 108 pp. 106482 -
Publisher
ELSEVIER SCIENCE INC