Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
1750 participants
INTERVENTIONAL
2018-07-19
2034-12-01
Brief Summary
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AIM: RAMPART is a phase III Multi-Arm Multi-Stage randomised controlled platform trial, initiated with three arms. The trial is assessing if durvalumab monotherapy or the combination of durvalumab and tremelimumab can improve Disease Free Survival (DFS) or Overall Survival (OS) compared to the current global standard-of-care (active monitoring). At the start of recruitment, patients with Leibovich scores 3 to 11 will be eligible for randomisation. Accrual of intermediate risk patients (Leibovich scores 3 5) will stop after 3 years or when intermediate risk patients contribute 25% of the total accrual target, whichever is earlier. Recruitment of patients with Leibovich scores 6 to 11 will continue until the accrual target is reached.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm B (durvalumab monotherapy)
Participants randomised to Arm B will receive durvalumab (1500mg) 4 weekly for 1 year (13 cycles maximum)
Durvalumab
controlled infusion via an infusion pump into a peripheral or central vein
Arm C (durvalumab + tremelimumab)
Participants randomised to Arm C will receive durvalumab (administered as per arm B, i.e. 13 cycles maximum) and tremelimumab (75mg) on day 1 and week 4 visits (i.e. 2 cycles)
Durvalumab
controlled infusion via an infusion pump into a peripheral or central vein
Tremelimumab
controlled infusion via an infusion pump into a peripheral or central vein
Arm A (active monitoring)
Participants randomised to Arm A will be allocated to active monitoring for 1 year, in line with current standard-of-care in resected primary RCC at high or intermediate risk of relapse
No interventions assigned to this group
Interventions
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Durvalumab
controlled infusion via an infusion pump into a peripheral or central vein
Tremelimumab
controlled infusion via an infusion pump into a peripheral or central vein
Eligibility Criteria
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Inclusion Criteria
2. At the start of recruitment patients with Leibovich score 3-11 will be eligible for randomisation. MRC CTU at UCL 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.
3. Patients should have had surgery at least 28 days but no more than 91 days prior to their randomisation date.
4. Post-operative scans should be performed within 28 days prior to randomisation.
5. 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.
6. WHO Performance Status 0 or 1.
7. Patient has archival FFPE pathology tissue available, and agrees to provide at least one sample (FFPE tumour block from nephrectomy, or a minimum of 10 unstained slides), as well as a baseline EDTA blood sample for future translational research).
8. Adequate normal organ and marrow function
1. Haemoglobin ≥9.0g/dL (transfusions will be allowed within 2 weeks prior to randomisation in order to achieve the entry criteria).
2. Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500 per mm3).
3. Platelet count ≥100 x 109 (≥100,000 per mm3).
4. Bilirubin ≤1.5 x ULN (This will not apply to subjects with confirmed Gilbert's syndrome (i.e., persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician).
5. AST/ALT ≤2.5 x ULN.
6. Calculated Creatinine Clearance level \>40mL/min by Cockcroft Gault formula (using actual body weight).
9. 12-lead ECG on which QTcF must be \<450 ms. In case of clinically significant ECG abnormalities, including a QTcF value ≥450 ms, two additional 12-lead ECGs should be obtained over a brief period (e.g., 30 minutes) to confirm the finding. Patients are only eligible if a QTcF of \<450ms is confirmed
10. Subjects must be ≥18 years of age.
11. Written informed consent obtained from the patient.
12. Both men and women enrolled in this trial must be in agreement with trial policy on contraception during the treatment phase of the study and 6 months afterwards. Egg donation, sperm donation and breastfeeding must be avoided.
13. Evidence of post-menopausal status or 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:
1. Women \<50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilisation (bilateral oophorectomy or hysterectomy).
2. Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy induced menopause with last menses \>1 year ago, or underwent surgical sterilisation (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
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.
7. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
8. History of leptomeningeal carcinomatosis.
9. 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.
10. 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.
11. 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.
12. 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 \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only after consultation with the RAMPART Trial Management Team
5. Patients with coeliac disease controlled by diet alone
13. A history of immunodeficiency syndrome. Please consult the MRC CTU at UCL on an individual basis if there is any uncertainty.
14. History of allogeneic organ transplant.
15. Uncontrolled intercurrent illness including, but not limited to:
1. Ongoing or active infection of any kind (patients who are exhibiting symptoms consistent with COVID-19, or who have tested positive, should not be randomised into the study until they are asymptomatic and at least 14 days after a positive test)
2. Symptomatic congestive heart failure
3. Uncontrolled hypertension
4. Unstable angina pectoris
5. Uncontrolled cardiac arrhythmia
6. Active peptic ulcer disease or gastritis
7. Active bleeding diatheses
8. Psychiatric illness or social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
16. Active infection including
1. Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
2. Hepatitis B (known positive HBV surface antigen (HBsAg) result). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti HBc\] and absence of HBsAg) are eligible.
3. Hepatitis C
4. Human immunodeficiency virus (positive HIV 1/2 antibodies). Note: Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
17. Receipt of live attenuated vaccine within 30 days prior to the start of treatment. Note: Patients, if enrolled, should not receive live vaccine while receiving investigational medicinal product and up to 30 days after the last dose of investigational medicinal product.
18. Pregnant or breastfeeding patients.
19. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
20. Known allergy or hypersensitivity to durvalumab or tremelimumab, or any of their excipients.
21. Previous investigational medicinal product assignment in the present study.
22. Clinically significant pneumonitis or fibrosis.
Exclusion Criteria
2. Metastatic or macroscopic residual disease.
3. Patients with positive resection margins after partial nephrectomy.
4. Patients with a single pulmonary nodule ≥5mm 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.
5. Prior anticancer treatment (other than nephrectomy) for RCC.
18 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Kidney Cancer UK
OTHER
Cancer Research UK
OTHER
University College, London
OTHER
Responsible Party
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Principal Investigators
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James Larkin
Role: PRINCIPAL_INVESTIGATOR
Royal Marsden NHS Foundation Trust
Locations
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Aberdeen Royal Infirmary
Aberdeen, , United Kingdom
Ysbyty Gwynedd
Bangor, , United Kingdom
Royal Bournemouth Hospital
Bournemouth, , United Kingdom
Bristol Haematology and Oncology Centre
Bristol, , United Kingdom
Addenbrookes Hospital
Cambridge, , United Kingdom
Velindre Cancer Centre
Cardiff, , United Kingdom
Broomfield Hospital
Chelmsford, , United Kingdom
Cheltenham General Hospital
Cheltenham, , United Kingdom
Colchester General Hospital
Colchester, , United Kingdom
University Hospital Coventry & Warwickshire
Coventry, , United Kingdom
Western General Hospital
Edinburgh, , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
Diana Princess of Wales Hospital
Grimsby, , United Kingdom
Castle Hill Hospital
Hull, , United Kingdom
Raigmore Hospital
Inverness, , United Kingdom
St James University Hospital
Leeds, , United Kingdom
Leicester Royal Infirmary
Leicester, , United Kingdom
Clatterbridge Cancer Centre
Liverpool, , United Kingdom
St Bartholomew's Hospital
London, , United Kingdom
Mount Vernon Hospital
London, , United Kingdom
Royal Free Hospital
London, , United Kingdom
Guy's Hospital
London, , United Kingdom
Royal Marsden Hospital
London, , United Kingdom
Charing Cross Hospital
London, , United Kingdom
The Christie
Manchester, , United Kingdom
Nottingham University Hospital
Nottingham, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Glan Clwyd Hospital
Rhyl, , United Kingdom
Scunthorpe General Hospital
Scunthorpe, , United Kingdom
Weston Park Hospital
Sheffield, , United Kingdom
South Tyneside District Hospital
South Shields, , United Kingdom
Southend University Hospital
Southend-on-Sea, , United Kingdom
Sunderland Royal Hospital
Sunderland, , United Kingdom
Royal Marsden Hospital
Sutton, , United Kingdom
Torbay Hospital
Torquay, , United Kingdom
Countries
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Central Contacts
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References
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Oza B, Frangou E, Smith B, Bryant H, Kaplan R, Choodari-Oskooei B, Powles T, Stewart GD, Albiges L, Bex A, Choueiri TK, Davis ID, Eisen T, Fielding A, Harrison D, McWhirter A, Mulhere S, Nathan P, Rini B, Ritchie A, Scovell S, Shakeshaft C, Stockler MR, Thorogood N, Parmar MKB, Larkin J, Meade A. 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. Contemp Clin Trials. 2021 Sep;108:106482. doi: 10.1016/j.cct.2021.106482. Epub 2021 Sep 16.
Meade A, Oza B, Frangou E, Smith B, Bryant H, Kaplan R, Choodari-Oskooei B, Powles T, Stewart GD, Albiges L, Bex A, Choueiri TK, Davis ID, Eisen T, Fielding A, Harrison DJ, McWhirter A, Mulhere S, Nathan P, Rini B, Ritchie A, Scovell S, Shakeshaft C, Stockler MR, Thorogood N, Larkin J, Parmar MKB. RAMPART: A model for a regulatory-ready academic-led phase III trial in the adjuvant renal cell carcinoma setting. Contemp Clin Trials. 2021 Sep;108:106481. doi: 10.1016/j.cct.2021.106481. Epub 2021 Sep 16.
Marconi L, Sun M, Beisland C, Klatte T, Ljungberg B, Stewart GD, Dabestani S, Choueiri TK, Bex A. Prevalence, Disease-free, and Overall Survival of Contemporary Patients With Renal Cell Carcinoma Eligible for Adjuvant Checkpoint Inhibitor Trials. Clin Genitourin Cancer. 2021 Apr;19(2):e92-e99. doi: 10.1016/j.clgc.2020.12.005. Epub 2021 Jan 7.
Other Identifiers
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MRC RE06
Identifier Type: -
Identifier Source: org_study_id
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