RAMPART Summary
|
Summary Information Type |
Summary Details |
|
Acronym/Short Title of Trial |
RAMPART - Renal Adjuvant MultiPle Arm Randomised Trial |
|
Long Title of Trial |
An international investigator-led phase III multi-arm multi-stage randomised-controlled platform trial of adjuvant therapy in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse. |
|
Version |
1.0 |
|
Date |
22/11/2017 |
|
MRC CTU at UCL ID |
RE06 |
|
ISRCTN # |
ISRCTN53348826 |
|
NCT # |
NCT03288532 |
|
EudraCT # |
2017-002329-39 |
|
CTA # |
20363/0380/001-0001 |
|
MREC # |
17/LO/1875 |
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Study Design |
RAMPART is a phase III multi-arm, multi-stage (MAMS), multi‑centre, randomised controlled platform trial. |
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Type of Participants to be Studied |
Patients who have had their RCC resected are eligible for randomisation into RAMPART. At the start of recruitment patients with Leibovich score 3-11 will be eligible for randomisation. We will monitor accrual and stop recruiting intermediate risk patients (Leibovich Score 3-5) after three years or when intermediate risk patients contribute 25% of the total accrual target, whichever is earlier. Recruitment of patients with Leibovich Score 6-11 will continue until the accrual target is reached. |
|
Setting |
RCC adjuvant therapy |
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Interventions to be Compared |
Patients will be randomly assigned to one of the following trial arms: – Arm A - active monitoring for 1 year – Arm B - durvalumab (1500mg) 4 weekly for 1 year (13 cycles) – Arm C - durvalumab (administered as per arm B, i.e., 13 cycles) and tremelimumab (75mg) on day 1 and week 4 visits (i.e., 2 cycles). |
|
Study Aims |
RAMPART has been designed to answer the following questions: 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) |
|
Study Hypothesis |
Durvalumab is able to prevent tumour relapse by the inhibition of the programmed cell death 1/programmed death ligand 1 pathway, which plays a critical role in tumour immune evasion. Combination treatment with anti-CTLA4 agent tremelimumab increases immune response and anti-tumour activity. |
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Co-Primary Outcome Measure(s) |
DFS and OS DFS is defined as the interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first. OS is defined as all-cause mortality, the time from randomisation to death from any cause (including RCC). |
|
Secondary Outcome Measure(s) |
Metastasis-free survival (MFS), i.e., the interval from randomisation to first evidence of metastases or death from RCC RCC specific survival time, i.e., the time from randomisation to death from RCC Quality of life Toxicity Patient preferences for adjuvant immunotherapy |
|
Randomisation |
Patients will be randomised centrally using the method of minimisation over a small number of clinically important stratification factors with an additional random element. |
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Number of Participants to be Studied |
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 study arms will be: – Arm A - 750 patients – Arm B - 500 patients – Arm C - 500 patients |
|
Duration |
The duration of treatment in each of research arms B and C is one year. We anticipate reporting on the co-primary outcomes as follows (all times are from the start of recruitment and assume that RAMPART will become a 4-arm trial before the initial 3 arms are reported): – DFS in the durvalumab/tremelimumab combination arm after approx. 6.25 years – DFS in the single-agent durvalumab arm after approx. 10.5 years – OS in high-risk patients (Leibovich Score 6-11) in the durvalumab/tremelimumab combination arm after approx. 13.25 years – OS in high-risk patients (Leibovich Score 6-11) in the single-agent durvalumab arm after approx. 20.25 years |
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Ancillary Studies/Sub studies |
Translational Sub-study
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Sponsor |
The RAMPART trial is an investigator-led academic trial sponsored by UCL and co-ordinated by the MRC CTU at UCL. |
|
Funders |
Kidney Cancer UK (clinical trial grant award) AstraZeneca LP (educational grant) |
|
Trial Managers |
Mr Ben Smith Dr Francesca Schiavone |
|
Chief Investigator |
Dr James Larkin |
|
MRC CTU at UCL Project Leader |
Dr Angela Meade |