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 Ritchie; Sarah Scovell; Clare Shakeshaft; Martin R Stockler; Nat Thorogood; Mahesh K B Parmar; James Larkin; Angela Meade

doi:10.1016/j.cct.2021.106482

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

Contemp Clin Trials. 2021 Sep:108:106482. doi: 10.1016/j.cct.2021.106482. Epub 2021 Sep 16.

Authors

Bhavna Oza¹, Eleni Frangou², Ben Smith², Hanna Bryant², Rick Kaplan², Babak Choodari-Oskooei², Tom Powles³, Grant D Stewart⁴, Laurence Albiges⁵, Axel Bex⁶, Toni K Choueiri⁷, Ian D Davis⁸, Tim Eisen⁹, Alison Fielding², David Harrison¹⁰, Anita McWhirter¹¹, Salena Mulhere², Paul Nathan¹², Brian Rini¹³, Alastair Ritchie², Sarah Scovell³, Clare Shakeshaft², Martin R Stockler¹⁴, Nat Thorogood², Mahesh K B Parmar², James Larkin¹¹, Angela Meade²

Affiliations

¹ MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London WC1V 6LJ, UK. Electronic address: b.oza@ucl.ac.uk.
² MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London WC1V 6LJ, UK.
³ St Bartholomew's Hospital, W Smithfield, London EC1A 7B, UK.
⁴ Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
⁵ Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
⁶ Royal Free London NHS Foundation Trust UCL Division of Surgery and Interventional Science, Pond Street, London NW3 2QG; Netherlands Cancer Institute, Amsterdam, the Netherlands.
⁷ Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, United States.
⁸ Monash University Eastern Health Clinical School, Level 2, 5 Arnold Street, Box Hill, VIC 3128, Australia; Department of Medical Oncology, Eastern Health, Melbourne, Australia; ANZUP Cancer Trials Group, Sydney, Australia.
⁹ Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge Biomedical Campus Hill's Road, Cambridge CB2 0QQ, UK.
¹⁰ University of St Andrews, North Haugh, St Andrews KY16 9TF, UK.
¹¹ Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London SW3 6JJ, UK.
¹² Mount Vernon Cancer Centre, Rickmansworth Rd, Northwood HA6 2RN, UK.
¹³ Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, United States.
¹⁴ ANZUP Cancer Trials Group, Sydney, Australia; NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW 2006, Australia.

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.

Keywords: Check-point inhibitor; Durvalumab; MAMS; Platform trial; RAMPART; Renal cancer; Tremelimumab.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell* / surgery
Chronic Disease
Humans
Kidney Neoplasms* / surgery
Quality of Life
Recurrence

Associated data

ClinicalTrials.gov/NCT03288532

Abstract

Publication types

MeSH terms

Associated data

Grants and funding