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 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.

PMID: 34538402
PMCID: PMC8520913
DOI: 10.1016/j.cct.2021.106482

Clinical Trial

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 et al. Contemp Clin Trials. 2021 Sep.

. 2021 Sep:108:106482.

doi: 10.1016/j.cct.2021.106482. Epub 2021 Sep 16.

Authors

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.

PMID: 34538402
PMCID: PMC8520913
DOI: 10.1016/j.cct.2021.106482

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.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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References

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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

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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

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