Resected primary renal cell carcinoma Cancer Malignant neoplasm of kidney, except renal pelvis
Conditions
Interventions
The trial will initially open with 3 research arms. The allocation ratio will be 3:2:2 with patients assigned centrally through block randomisation with a small number of clinically important stratifi
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 11/02/2026: 1. Histologically proven RCC (all cell types of RCC are eligible, except for pure oncocytoma, collecting duct, medullary and transitional cell cancer [TCC]); no evidence of residual macroscopic disease on post-operative CT scan after resection of RCC. Patients with treated bilateral synchronous RCCs are eligible 2. At the start of recruitment, patients with a Leibovich score of 3-11 will be eligible for randomisation. MRC CTU at UCL will monitor accrual and stop recruiting intermediate risk patients (Leibovich Score 3-5) once agreed by the RAMPART TMG. Intermediate risk patients will contribute up to 25% of the total accrual target. Recruitment of patients with Leibovich Score 6-11 will continue until the accrual target is reached. 3. Patients with synchronous ipsilateral adrenal metastases will be eligible, provided they are fully resected (adrenal metastectomy) at the time of nephrectomy and there is no evidence of residual macroscopic disease on post-operative CT scans 4. Patients with a single soft tissue metastasis developing at any organ site will be eligible, provided they are fully resected (metastectomy) between 6-24 months after nephrectomy and there is no evidence of residual macroscopic disease on post-metastectomy CT scans 5. Patients should have had surgery (nephrectomy or metastectomy) at least 28 days but no more than 91 days prior to their randomisation date 6. Post-operative scans should be performed within 28 days prior to randomisation 7. Patients with microscopically positive resection margins after radical nephrectomy at the nephrectomy bed, renal vein or inferior vena cava are eligible, provided the post-operative CT scan shows no evidence of residual macroscopic disease 8. WHO Performance Status 0 or 1 9. Patient has archival FFPE pathology tissue available, and agrees to provide at least one sample (FFPE tumour block from nephrectomy and, where applicable, the adrenal metastectomy, or a minimum of 10 unstained slides), as well as baseline CPDA and PAXgene blood samples for future translational research (this is separate to providing consent for TransRAMPART) 10. Adequate normal organ and marrow function 11. Subjects must be =18 years of age 12. Written informed consent obtained from the patient 13. Both men and women enrolled in this trial must be in agreement with the trial policy on contraception during the treatment phase of the study and 6 months afterwards. Egg donation, sperm donation and breastfeeding must be avoided. 14. Evidence of post-menopausal status or a negative serum HCG pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply: 14.1. Women 1 year ago, had chemotherapy-induced menopause with last menses >1 year ag
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 11/02/2026: 1. Previous diagnosis of RCC 2. Metastatic disease except: 2.1. Synchronous ipsilateral adrenal metastases, which are fully resected at the time of nephrectomy 2.2. A single soft tissue metastasis developing at any organ site that has been fully resected between 6-24 months after radical nephrectomy 3. Macroscopic residual disease following nephrectomy 4. Patients with positive resection margins after partial nephrectomy. If multiple resection margins are taken, the patient will be considered eligible as long as the last margin is negative. 5. Patients with a single pulmonary nodule =5mm in diameter are not eligible unless the nodule has had a definite benign diagnosis. Patients with multiple small, less than 5 mm nodules may be eligible if nodules have been shown to be radiologically stable for at least 8 weeks. 6. Prior anticancer treatment (other than nephrectomy) for RCC 7. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria 7.1. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 7.2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician 8. Previous invasive or non-invasive malignancy except: 8.1. Basal cell carcinoma, where treatment consisted of resection alone or radiotherapy. 8.2. Low-grade non-muscle-invasive bladder carcinoma where treatment consisted of endoscopic resection alone or with a single installation of intravesical chemotherapy or with BCG treatment. 8.3. Ductal carcinoma in situ of the breast, where treatment consisted of resection alone. 8.4. Cervical carcinoma in situ where treatment consisted of resection alone. 8.5. Previously treated clinically localized low- or intermediate-risk prostate cancer with undetectable PSA after surgery or stable PSA for radiation therapy 8.6. Malignancy treated with curative intent and with no known active disease > 5 years before the first dose of IP and of low potential risk of recurrence 8.7. Other cancers with very low potential of recurrence can be discussed with MRC CTU at UCL, where eligibility will be considered on an individual basis 9. History of leptomeningeal carcinomatosis 10. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 11. Major surgical procedure (as defined by the Investigator) within 28 days prior to the start of treatment. Local surgery of isolated lesions for palliative intent is acceptable 12. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid 13. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, et
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Updated 11/02/2026. Previous primary outcome: 1. Disease-Free Survival (DFS) will be assessed via radiological assessments through CT scans. 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. All CT scans received will be further assessed by an independent review panel to ensure that progression has been reported correctly. Primary analysis for DFS will be carried out when: Arm C vs Arm A 276 control arm events (approx 6.25 years) have occurred Arm B vs Arm A 416 control arm events (approx 10.75 years) have occurred DFS Interim analysis will be carried out at the following timepoints: Arm B vs Arm A Interim analysis 1 (overwhelming and lack-of-benefit) when 197 control arm events have occurred (approx 4.75 years) Interim analysis 2 (overwhelming and lack-of-benefit) when 277 control arm events have occurred (approx 6.25 years) Interim analysis 3 (overwhelming benefit) when 332 control arm events have occurred (approx 8 years) Arm C vs Arm A: Interim analysis 1 (overwhelming benefit and lack-of-benefit) when 198 control arm events have occurred (approx 4.75 years) 2. Overall Survival (OS) is another co-primary endpoint. OS is defined as all cause mortality, the time from randomisation to death from any cause (including RCC). For UK sites, survival status will also be collected against national mortality registers. Comparison of overall survival for Arm B vs Arm A will be carried out at approximately 20.5 years after trial commencement (triggered by 344 control arm OS events). For Arm C vs Arm A, overall survival will be assessed at approximately 13.25 years after trial commences (triggered by 238 control arm OS events) | — |
Secondary
| Measure | Time frame |
|---|---|
| Updated 11/02/2026. Previous secondary outcomes: Assessment of all secondary outcomes will take place at each follow-up visit at week 52, then 3 monthly up to the end of year 3, 6-monthly up to year 5 and annually thereafter. 1. Metastasis-free survival (MFS), defined as the interval from randomisation to first evidence of metastasis or death from RCC, measured via radiological means (CT scan with contrast) 2. RCC-specific survival time, defined as the time from randomisation to death from RCC, reported on trial-specific CRF 3. Quality of life, measured using quality of life questionnaires (EQ-5D and QLQ-C30 CRFs) at baseline, week 16, month 15, month 36 visits and at progression (if progression occurs before month 36) 4. Toxicity, reported on trial-specific CRF 5. Patient preferences for adjuvant immunotherapy information collected through the optional PAIR questionnaire completed at baseline, at the week 12 visit and the month 15 visit, or approximately 3 months after the last treatment visit if patient stops treatment early Secondary outcome measures will be assessed after the primary analysis and therefore will be confirmed at a later date | — |
Countries
Australia, England, France, Scotland, Spain, United Kingdom, Wales
Contacts
Public ContactBen;Hanna Smith;Bryant
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Outcome results
None listed