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

• Published in: Contemporary clinical trials 2021-09, Vol.108, p.106482, Article 106482
• Main Authors: Oza, Bhavna, Frangou, Eleni, Smith, Ben, Bryant, Hanna, Kaplan, Rick, Choodari-Oskooei, Babak, Powles, Tom, Stewart, Grant D., Albiges, Laurence, Bex, Axel, Choueiri, Toni K., Davis, Ian D., Eisen, Tim, Fielding, Alison, Harrison, David, McWhirter, Anita, Mulhere, Salena, Nathan, Paul, Rini, Brian, Ritchie, Alastair, Scovell, Sarah, Shakeshaft, Clare, Stockler, Martin R., Thorogood, Nat, Parmar, Mahesh K.B., Larkin, James, Meade, Angela
• Format: Article
• Language: English
• Subjects: Carcinoma, Renal Cell - surgery; Check-point inhibitor; Chronic Disease; Durvalumab; Humans; Kidney Neoplasms - surgery; MAMS; Platform trial; Quality of Life; RAMPART; Recurrence; Renal cancer; Tremelimumab
• ISSN: 1551-7144; 1559-2030; 1559-2030
• DOI: 10.1016/j.cct.2021.106482

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. 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). 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. •RAMPART is the first international, academically led adjuvant trial to assess both single and combination immune checkpoint inhibitors in patients with RCC at intermediate and high risk of recurrence after nephrectomy.•RAMPART is a three arm adaptive MAMS platform trial upon which at least one new research arm can be added over the coming years.•The target population is participants with histologically proven RCC (clear cell and non-clear