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Renal Cell CarcinomaPhase 3RAMPARTNCT03288532

Renal Adjuvant MultiPle Arm Randomised Trial

A Phase 3 study testing Durvalumab and Tremelimumab in people with Renal Cell Carcinoma, run by University College, London at 35 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

RATIONALE: The current global standard of care after nephrectomy for localised RCC therefore remains active monitoring (i.e., observation by clinical and radiological means). 30-40% patients with initially localised RCC develop metastatic disease following nephrectomy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Durvalumab and Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,750 participants
Where
35 sitesUnited Kingdom
Study dates
19 Jul 2018to 1 Dec 2034
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • Patients should have had surgery at least 28 days but no more than 91 days prior to their randomisation date.
  • Post-operative scans should be performed within 28 days prior to randomisation.
  • 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.
  • WHO Performance Status 0 or 1.
Show all 21Show fewer
  • 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).
  • Adequate normal organ and marrow function
  • Haemoglobin ≥9.0g/dL (transfusions will be allowed within 2 weeks prior to randomisation in order to achieve the entry criteria).
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500 per mm3).
  • Platelet count ≥100 x 109 (≥100,000 per mm3).
  • 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).
  • AST/ALT ≤2.5 x ULN.
  • Calculated Creatinine Clearance level >40mL/min by Cockcroft Gault formula (using actual body weight).
  • 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
  • Subjects must be ≥18 years of age.
  • Written informed consent obtained from the patient.
  • 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.
  • 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:
  • 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).
  • 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).

Who cannot join

  • Previous diagnosis of RCC.
  • Metastatic or macroscopic residual disease.
  • Patients with positive resection margins after partial nephrectomy.
  • 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.
  • Prior anticancer treatment (other than nephrectomy) for RCC.
  • 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
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  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • 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.
  • History of another primary malignancy except for:
  • 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.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
  • History of leptomeningeal carcinomatosis.
  • 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.
  • 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.
  • 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.
  • 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:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the RAMPART Trial Management Team
  • Patients with coeliac disease controlled by diet alone
  • A history of immunodeficiency syndrome. Please consult the MRC CTU at UCL on an individual basis if there is any uncertainty.
  • History of allogeneic organ transplant.
  • Uncontrolled intercurrent illness including, but not limited to:
  • 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)
  • Symptomatic congestive heart failure
  • Uncontrolled hypertension
  • Unstable angina pectoris
  • Uncontrolled cardiac arrhythmia
  • Active peptic ulcer disease or gastritis
  • Active bleeding diatheses
  • Psychiatric illness or social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  • Active infection including
  • Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
  • 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.
  • Hepatitis C
  • 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.
  • 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.
  • Pregnant or breastfeeding patients.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  • Known allergy or hypersensitivity to durvalumab or tremelimumab, or any of their excipients.
  • Previous investigational medicinal product assignment in the present study.
  • Clinically significant pneumonitis or fibrosis.

Trial locations and contacts

35 sites in 1 country. Contact the study team or a site near you to ask about taking part.

RAMPART Trial Management Team contact

0044(0)207 670 ext. 4683/4743

mrcctu.rampart@ucl.ac.uk

35 sites in 1 country

United Kingdom35 sites, 35 recruiting

  • Aberdeen Royal Infirmary

    Aberdeen, AB25 2ZN

    Gordon Urquhart

    Recruiting

  • Ysbyty Gwynedd

    Bangor, LL57 2PW

    Pasquale Innominato

    Recruiting

  • Royal Bournemouth Hospital

    Bournemouth, BH7 7DW

    Tom Geldart

    Recruiting

  • Bristol Haematology and Oncology Centre

    Bristol, BS2 8ED

    Amit Bahl

    Recruiting

  • Addenbrookes Hospital

    Cambridge, CB2 0QQ

    Sarah Welsh

    Recruiting

  • Velindre Cancer Centre

    Cardiff, CF14 2TL

    Jim Barber

    Recruiting

  • Broomfield Hospital

    Chelmsford, CM1 7ET

    Gopalakrishnan Srinivasan

    Recruiting

  • Cheltenham General Hospital

    Cheltenham, GL53 7AN

    Marios Decatris

    Recruiting

  • Colchester General Hospital

    Colchester, CO4 5JL

    Muthu Kumar

    Recruiting

  • University Hospital Coventry & Warwickshire

    Coventry, CV2 2DX

    Yakhub Khan

    Recruiting

  • Western General Hospital

    Edinburgh, EH4 2XU

    Jahangeer Malik

    Recruiting

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

    Balaji Venugopal

    Recruiting

  • Diana Princess of Wales Hospital

    Grimsby, DN33 2BA

    Iqtedar Muazzam

    Recruiting

  • Castle Hill Hospital

    Hull, HU16 5JQ

    Anthony Maraveyas

    Recruiting

  • Raigmore Hospital

    Inverness, IV2 3UJ

    Neil McPhail

    Recruiting

  • St James University Hospital

    Leeds, LS9 7TF

    Naveen Vasudev

    Recruiting

  • Leicester Royal Infirmary

    Leicester, LE1 5WW

    Guy Faust

    Recruiting

  • Clatterbridge Cancer Centre

    Liverpool, L9 7AL

    Richard Griffiths

    Recruiting

  • St Bartholomew's Hospital

    London, EC1A 7BE

    Tom Powles

    Recruiting

  • Mount Vernon Hospital

    London, HA6 2RN

    Anand Sharma

    Recruiting

  • Royal Free Hospital

    London, NW3 2QG

    Ekaterini Boleti

    Recruiting

  • Guy's Hospital

    London, SE1 9RT

    Sarah Rudman

    Recruiting

  • Royal Marsden Hospital

    London, SW3 6JJ

    James Larkin

    Recruiting

  • Charing Cross Hospital

    London, W6 8RF

    Naveed Sarwar

    Recruiting

  • The Christie

    Manchester, M20 4BX

    Tom Waddell

    Recruiting

  • Nottingham University Hospital

    Nottingham, NG5 1PB

    Poulam Patel

    Recruiting

  • Churchill Hospital

    Oxford, OX3 7LE

    Andrew Protheroe

    Recruiting

  • Glan Clwyd Hospital

    Rhyl, LL18 5UJ

    Carey MacDonald Smith

    Recruiting

  • Scunthorpe General Hospital

    Scunthorpe, DN15 7BH

    George Bozas

    Recruiting

  • Weston Park Hospital

    Sheffield, S10 2SJ

    Carmel Pezaro

    Recruiting

  • South Tyneside District Hospital

    South Shields, NE34 0PL

    Ashraf Azzabi

    Recruiting

  • Southend University Hospital

    Southend-on-Sea, SS0 0RY

    Awais Jalil

    Recruiting

  • Sunderland Royal Hospital

    Sunderland, SR4 7TP

    Ashraf Azzabi

    Recruiting

  • Royal Marsden Hospital

    Sutton, SM2 5PT

    James Larkin

    Recruiting

  • Torbay Hospital

    Torquay, TQ2 7AA

    Anna Lydon

    Recruiting

Other trials in United Kingdom

About this study

Official title: An International Investigator-led Phase III Multi Arm Multi Stage Multi-centre Randomised Controlled Platform Trial of Adjuvant Therapy in Patients With Resected Primary Renal Cell Carcinoma (RCC) at High or Intermediate Risk of Relapse

RATIONALE: The current global standard of care after nephrectomy for localised RCC therefore remains active monitoring (i.e., observation by clinical and radiological means). 30-40% patients with initially localised RCC develop metastatic disease following nephrectomy. Need for adjuvant therapy is most marked in the high risk population where outcomes are predictably poor. However, the risk of recurrence in patients who are of intermediate risk of recurrence is not insignificant. Unfortunately, despite showing efficacy in advanced RCC, the results in the adjuvant setting, so far, are inconclusive.

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.

Being tested
Durvalumab, Tremelimumab
Keywords
Renal Cell Carcinoma, Immunotherapy, Multi-Arm Multi-Stage
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    controlled infusion via an infusion pump into a peripheral or central vein

  • TremelimumabDrug

    controlled infusion via an infusion pump into a peripheral or central vein

Study groups in NCT03288532
Study groupRoleWhat they receive
Arm A (active monitoring)No interventionParticipants 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
Arm B (durvalumab monotherapy)ExperimentalParticipants randomised to Arm B will receive durvalumab (1500mg) 4 weekly for 1 year (13 cycles maximum)
Receives: Drug: Durvalumab
Arm C (durvalumab + tremelimumab)ExperimentalParticipants 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)
Receives: Drug: Durvalumab; Drug: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival (DFS): Arm C vs A

    Interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first.

    Measured: 6.25 years

  2. Disease Free Survival (DFS): Arm B vs A

    Interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first.

    Measured: 10.54 years

  3. Overall Survival (OS): Arm C vs A (high risk patients only)

    All-cause mortality, the time from randomisation to death from any cause (including RCC).

    Measured: 13.25 years

  4. Overall Survival (OS): Arm B vs A (high risk patients only)

    All-cause mortality, the time from randomisation to death from any cause (including RCC).

    Measured: 20.5 years

Secondary outcomes (4)

  1. Metastasis-free survival (MFS): Arm C vs A

    Interval from randomisation to first evidence of metastases or death from RCC

    Measured: 6.25 years

  2. Metastasis-free survival (MFS): Arm B vs A

    Interval from randomisation to first evidence of metastases or death from RCC

    Measured: 10.54 years

  3. RCC specific survival time: Arm C vs A

    Time from randomisation to death from RCC

    Measured: 13.25 years

  4. RCC specific survival time: Arm C vs A

    Time from randomisation to death from RCC

    Measured: 20.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2017
  2. Study start19 Jul 2018
  3. Primary completion1 Jul 2024 (estimated)
  4. Study completion1 Dec 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multi-Arm Multi-Stage Design
Masking
None (open label)
Enrolment
1,750 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03288532
Sponsor's protocol ID
MRC RE06
Acronym
RAMPART
Status last verified
Sep 2020
First submitted
4 Sep 2017
Last updated
7 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 34538402

  • 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.

    PubMed 34538401

  • 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.

    PubMed 33526329

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Durvalumab and Tremelimumab in people with Renal Cell Carcinoma, run by University College, London at 35 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact RAMPART Trial Management Team (0044(0)207 670 ext. 4683/4743, mrcctu.rampart@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (DFS): Arm C vs A (time frame: 6.25 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03288532, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2020.

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