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

Who is this study for? Patients with resected primary renal cell carcinoma who are high or intermediate risk of relapse
Status: Recruiting
Location: See all (35) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
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. 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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

• 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).

Locations
Other Locations
United Kingdom
Aberdeen Royal Infirmary
RECRUITING
Aberdeen
Ysbyty Gwynedd
RECRUITING
Bangor
Royal Bournemouth Hospital
RECRUITING
Bournemouth
Bristol Haematology and Oncology Centre
RECRUITING
Bristol
Addenbrookes Hospital
RECRUITING
Cambridge
Velindre Cancer Centre
RECRUITING
Cardiff
Broomfield Hospital
RECRUITING
Chelmsford
Cheltenham General Hospital
RECRUITING
Cheltenham
Colchester General Hospital
RECRUITING
Colchester
University Hospital Coventry & Warwickshire
RECRUITING
Coventry
Western General Hospital
RECRUITING
Edinburgh
Beatson West of Scotland Cancer Centre
RECRUITING
Glasgow
Diana Princess of Wales Hospital
RECRUITING
Grimsby
Castle Hill Hospital
RECRUITING
Hull
Raigmore Hospital
RECRUITING
Inverness
St James University Hospital
RECRUITING
Leeds
Leicester Royal Infirmary
RECRUITING
Leicester
Clatterbridge Cancer Centre
RECRUITING
Liverpool
Charing Cross Hospital
RECRUITING
London
Guy's Hospital
RECRUITING
London
Mount Vernon Hospital
RECRUITING
London
Royal Free Hospital
RECRUITING
London
Royal Marsden Hospital
RECRUITING
London
St Bartholomew's Hospital
RECRUITING
London
The Christie
RECRUITING
Manchester
Nottingham University Hospital
RECRUITING
Nottingham
Churchill Hospital
RECRUITING
Oxford
Glan Clwyd Hospital
RECRUITING
Rhyl
Scunthorpe General Hospital
RECRUITING
Scunthorpe
Weston Park Hospital
RECRUITING
Sheffield
South Tyneside District Hospital
RECRUITING
South Shields
Southend University Hospital
RECRUITING
Southend-on-sea
Sunderland Royal Hospital
RECRUITING
Sunderland
Royal Marsden Hospital
RECRUITING
Sutton
Torbay Hospital
RECRUITING
Torquay
Contact Information
Primary
RAMPART Trial Management Team
mrcctu.rampart@ucl.ac.uk
0044(0)207 670
Time Frame
Start Date: 2018-07-19
Estimated Completion Date: 2034-12-01
Participants
Target number of participants: 1750
Treatments
No_intervention: 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
Experimental: Arm B (durvalumab monotherapy)
Participants randomised to Arm B will receive durvalumab (1500mg) 4 weekly for 1 year (13 cycles maximum)
Experimental: 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)
Related Therapeutic Areas
Sponsors
Collaborators: Kidney Cancer UK, Cancer Research UK, AstraZeneca
Leads: University College, London

This content was sourced from clinicaltrials.gov

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