Renal Adjuvant MultiPle Arm Randomised Trial, or RAMPART, is a phase III multi-arm multi-stage randomised controlled platform trial, initiated with a three-arm design. The proposed interventions will be given as an adjuvant therapy to individuals who have had surgically removed localised renal cell carcinoma.
Renal cell carcinoma (RCC) is the 8th most common cancer in the UK with a growing increase in incidence. In 2011/ 12, incidence in the UK was 10,144 individuals and 338,000 globally. There is significant mortality observed in the young-middle age category in particular.
The current global standard of care after nephrectomy for localised RCC is active monitoring (i.e. observation by clinical and radiological means). 30-40% patients with initially localised RCC develop metastatic disease following nephrectomy. Currently, no adjuvant therapy has proven benefit. A requirement for adjuvant therapy is most marked in the high risk population where outcomes are predictably poor. An effective adjuvant therapy should prevent disease recurrence with the ultimate aim of prolonging survival.
The drugs being used in RAMPART are Durvalumab and Tremelimumab. These drugs belong to a type of treatment group known as immunotherapy and work by helping a patient's immune system attack their cancer. Durvalumab, which can also be referred to as an anti-PDL1 drug, is currently being tested as both a single therapy and as part of combinational therapies in many cancer types. Early indications have shown that it works well and has controllable side effects. Tremelimumab is often referred to as an anti-CTLA4 drug. Treatment with Tremelimumab has proven efficacy in treatment of a number of different cancer types, especially in combination with other cancer treatments. Recent studies have also shown this combinational therapy to be safe in the treatment of lung cancer.
RAMPART will be co-ordinated by the Medical Research Council (MRC) Clinical Trials Unit based in London.
Aims and Objectives
The RAMPART platform trials has been designed to evaluate multiple treatments simultaneously while adapting to a changing landscape as data on different agents and combinations of agents emerge.
The aims for the initial research comparisons are as follows:
- Does treatment with either durvalumab alone or a combination of durvalumab and tremelimumab increase Disease Free Survival (DFS) compared with active monitoring (Arm B vs Arm A, and Arms C vs Arm A respectively)?
- Does treatment with either durvalumab alone or a combination of durvalumab and tremelimumab increase Overall Survival (OS) compared with active monitoring in patients classified as Leibovich high-risk (Arm B vs Arm A, and Arms C vs Arm A respectively).
RAMPART will utilise three arms; Arm A: active monitoring, Arm B: Durvalumab and Arm C: Durvalumab and Tremelimumab; with treatment administered over the course of a year. Once patients are deemed eligible they are randomised into one of three arms. Throughout the course of the trial, participants are regularly monitored through follow-up checks assessing safety and efficacy of therapies used.
Overall Trial Management: RAMPART is managed by the Medical Research Council (MRC) Clinical Trials Unit.
Trial sponsor: RAMPART is sponsored by University College London (UCL).
Funding: RAMPART is jointly funded by AstraZeneca and Kidney Cancer UK.
Approximately 1750 patients will be recruited to the current three arm design. As RAMPART is an adaptive, platform trial we plan to add at least one additional arm over time.
Recruitment across the current three arms will be:
- Arm A - 750 patients
- Arm B - 500 patients
- Arm C - 500 patients