<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03288532</url>
  </required_header>
  <id_info>
    <org_study_id>MRC RE06</org_study_id>
    <nct_id>NCT03288532</nct_id>
  </id_info>
  <brief_title>Renal Adjuvant MultiPle Arm Randomised Trial</brief_title>
  <acronym>RAMPART</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kidney Cancer UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      RATIONALE: The current global standard of care after nephrectomy for localised RCC therefore&#xD;
      remains active monitoring (i.e., observation by clinical and radiological means). 30-40%&#xD;
      patients with initially localised RCC develop metastatic disease following nephrectomy. Need&#xD;
      for adjuvant therapy is most marked in the high risk population where outcomes are&#xD;
      predictably poor. However, the risk of recurrence in patients who are of intermediate risk of&#xD;
      recurrence is not insignificant. Unfortunately, despite showing efficacy in advanced RCC, the&#xD;
      results in the adjuvant setting, so far, are inconclusive.&#xD;
&#xD;
      AIM: RAMPART is a phase III Multi-Arm Multi-Stage randomised controlled platform trial,&#xD;
      initiated with three arms. The trial is assessing if durvalumab monotherapy or the&#xD;
      combination of durvalumab and tremelimumab can improve Disease Free Survival (DFS) or Overall&#xD;
      Survival (OS) compared to the current global standard-of-care (active monitoring). At the&#xD;
      start of recruitment, patients with Leibovich scores 3 to 11 will be eligible for&#xD;
      randomisation. Accrual of intermediate risk patients (Leibovich scores 3 5) will stop after 3&#xD;
      years or when intermediate risk patients contribute 25% of the total accrual target,&#xD;
      whichever is earlier. Recruitment of patients with Leibovich scores 6 to 11 will continue&#xD;
      until the accrual target is reached.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 19, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2034</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Multi-Arm Multi-Stage Design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Free Survival (DFS): Arm C vs A</measure>
    <time_frame>6.25 years</time_frame>
    <description>Interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease Free Survival (DFS): Arm B vs A</measure>
    <time_frame>10.54 years</time_frame>
    <description>Interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS): Arm C vs A (high risk patients only)</measure>
    <time_frame>13.25 years</time_frame>
    <description>All-cause mortality, the time from randomisation to death from any cause (including RCC).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS): Arm B vs A (high risk patients only)</measure>
    <time_frame>20.5 years</time_frame>
    <description>All-cause mortality, the time from randomisation to death from any cause (including RCC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Metastasis-free survival (MFS): Arm C vs A</measure>
    <time_frame>6.25 years</time_frame>
    <description>Interval from randomisation to first evidence of metastases or death from RCC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metastasis-free survival (MFS): Arm B vs A</measure>
    <time_frame>10.54 years</time_frame>
    <description>Interval from randomisation to first evidence of metastases or death from RCC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RCC specific survival time: Arm C vs A</measure>
    <time_frame>13.25 years</time_frame>
    <description>Time from randomisation to death from RCC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RCC specific survival time: Arm C vs A</measure>
    <time_frame>20.5 years</time_frame>
    <description>Time from randomisation to death from RCC</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">1750</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A (active monitoring)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (durvalumab monotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomised to Arm B will receive durvalumab (1500mg) 4 weekly for 1 year (13 cycles maximum)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C (durvalumab + tremelimumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>controlled infusion via an infusion pump into a peripheral or central vein</description>
    <arm_group_label>Arm B (durvalumab monotherapy)</arm_group_label>
    <arm_group_label>Arm C (durvalumab + tremelimumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab</intervention_name>
    <description>controlled infusion via an infusion pump into a peripheral or central vein</description>
    <arm_group_label>Arm C (durvalumab + tremelimumab)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically proven RCC (all cell types of RCC are eligible, except for pure&#xD;
             oncocytoma, collecting duct, medullary and transitional cell cancer [TCC]); no&#xD;
             evidence of residual macroscopic disease on post-operative CT scan after resection of&#xD;
             RCC. Patients with treated bilateral synchronous RCCs are eligible.&#xD;
&#xD;
          2. At the start of recruitment patients with Leibovich score 3-11 will be eligible for&#xD;
             randomisation. MRC CTU at UCL will monitor accrual and stop recruiting intermediate&#xD;
             risk patients (Leibovich Score 3-5) after three years or when intermediate risk&#xD;
             patients contribute 25% of the total accrual target, whichever is earlier. Recruitment&#xD;
             of patients with Leibovich Score 6 11 will continue until the accrual target is&#xD;
             reached.&#xD;
&#xD;
          3. Patients should have had surgery at least 28 days but no more than 91 days prior to&#xD;
             their randomisation date.&#xD;
&#xD;
          4. Post-operative scans should be performed within 28 days prior to randomisation.&#xD;
&#xD;
          5. Patients with microscopically positive resection margins after radical nephrectomy at&#xD;
             the nephrectomy bed, renal vein or inferior vena cava are eligible provided the&#xD;
             post-operative CT scan shows no evidence of residual macroscopic disease.&#xD;
&#xD;
          6. WHO Performance Status 0 or 1.&#xD;
&#xD;
          7. Patient has archival FFPE pathology tissue available, and agrees to provide at least&#xD;
             one sample (FFPE tumour block from nephrectomy, or a minimum of 10 unstained slides),&#xD;
             as well as a baseline EDTA blood sample for future translational research).&#xD;
&#xD;
          8. Adequate normal organ and marrow function&#xD;
&#xD;
               1. Haemoglobin ≥9.0g/dL (transfusions will be allowed within 2 weeks prior to&#xD;
                  randomisation in order to achieve the entry criteria).&#xD;
&#xD;
               2. Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500 per mm3).&#xD;
&#xD;
               3. Platelet count ≥100 x 109 (≥100,000 per mm3).&#xD;
&#xD;
               4. Bilirubin ≤1.5 x ULN (This will not apply to subjects with confirmed Gilbert's&#xD;
                  syndrome (i.e., persistent or recurrent hyperbilirubinemia that is predominantly&#xD;
                  unconjugated in the absence of haemolysis or hepatic pathology), who will be&#xD;
                  allowed only in consultation with their physician).&#xD;
&#xD;
               5. AST/ALT ≤2.5 x ULN.&#xD;
&#xD;
               6. Calculated Creatinine Clearance level &gt;40mL/min by Cockcroft Gault formula (using&#xD;
                  actual body weight).&#xD;
&#xD;
          9. 12-lead ECG on which QTcF must be &lt;450 ms. In case of clinically significant ECG&#xD;
             abnormalities, including a QTcF value ≥450 ms, two additional 12-lead ECGs should be&#xD;
             obtained over a brief period (e.g., 30 minutes) to confirm the finding. Patients are&#xD;
             only eligible if a QTcF of &lt;450ms is confirmed&#xD;
&#xD;
         10. Subjects must be ≥18 years of age.&#xD;
&#xD;
         11. Written informed consent obtained from the patient.&#xD;
&#xD;
         12. Both men and women enrolled in this trial must be in agreement with trial policy on&#xD;
             contraception during the treatment phase of the study and 6 months afterwards. Egg&#xD;
             donation, sperm donation and breastfeeding must be avoided.&#xD;
&#xD;
         13. Evidence of post-menopausal status or negative serum HCG pregnancy test for female pre&#xD;
             menopausal patients. Women will be considered post-menopausal if they have been&#xD;
             amenorrhoeic for 12 months without an alternative medical cause. The following age&#xD;
             specific requirements apply:&#xD;
&#xD;
               1. Women &lt;50 years of age will be considered post-menopausal if they have been&#xD;
                  amenorrhoeic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and if they have luteinising hormone and follicle-stimulating hormone&#xD;
                  levels in the post-menopausal range for the institution or underwent surgical&#xD;
                  sterilisation (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
               2. Women ≥50 years of age will be considered post-menopausal if they have been&#xD;
                  amenorrhoeic for 12 months or more following cessation of all exogenous hormonal&#xD;
                  treatments, had radiation-induced menopause with last menses &gt;1 year ago, had&#xD;
                  chemotherapy induced menopause with last menses &gt;1 year ago, or underwent&#xD;
                  surgical sterilisation (bilateral oophorectomy, bilateral salpingectomy, or&#xD;
                  hysterectomy).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous diagnosis of RCC.&#xD;
&#xD;
          2. Metastatic or macroscopic residual disease.&#xD;
&#xD;
          3. Patients with positive resection margins after partial nephrectomy.&#xD;
&#xD;
          4. Patients with a single pulmonary nodule ≥5mm diameter are not eligible unless the&#xD;
             nodule has had a definite benign diagnosis. Patients with multiple small, less than 5&#xD;
             mm nodules may be eligible if nodules have been shown to be radiologically stable for&#xD;
             at least 8 weeks.&#xD;
&#xD;
          5. Prior anticancer treatment (other than nephrectomy) for RCC.&#xD;
&#xD;
          6. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria&#xD;
&#xD;
               1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after&#xD;
                  consultation with the Study Physician.&#xD;
&#xD;
               2. Patients with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
                  treatment with durvalumab or tremelimumab may be included only after consultation&#xD;
                  with the Study Physician.&#xD;
&#xD;
          7. History of another primary malignancy except for:&#xD;
&#xD;
               1. Malignancy treated with curative intent and with no known active disease ≥5 years&#xD;
                  before the first dose of IP and of low potential risk for recurrence.&#xD;
&#xD;
               2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease.&#xD;
&#xD;
               3. Adequately treated carcinoma in situ without evidence of disease.&#xD;
&#xD;
          8. History of leptomeningeal carcinomatosis.&#xD;
&#xD;
          9. Concurrent enrolment in another clinical study, unless it is an observational (non&#xD;
             interventional) clinical study or during the follow up period of an interventional&#xD;
             study.&#xD;
&#xD;
         10. Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             start of treatment. Local surgery of isolated lesions for palliative intent is&#xD;
             acceptable.&#xD;
&#xD;
         11. Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled&#xD;
             corticosteroids or systemic corticosteroids at physiological doses, which are not to&#xD;
             exceed 10 mg/day of prednisone, or an equivalent corticosteroid.&#xD;
&#xD;
         12. Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with&#xD;
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,&#xD;
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               1. Patients with vitiligo or alopecia&#xD;
&#xD;
               2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on&#xD;
                  hormone replacement&#xD;
&#xD;
               3. Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
               4. Patients without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the RAMPART Trial Management Team&#xD;
&#xD;
               5. Patients with coeliac disease controlled by diet alone&#xD;
&#xD;
         13. A history of immunodeficiency syndrome. Please consult the MRC CTU at UCL on an&#xD;
             individual basis if there is any uncertainty.&#xD;
&#xD;
         14. History of allogeneic organ transplant.&#xD;
&#xD;
         15. Uncontrolled intercurrent illness including, but not limited to:&#xD;
&#xD;
               1. Ongoing or active infection of any kind (patients who are exhibiting symptoms&#xD;
                  consistent with COVID-19, or who have tested positive, should not be randomised&#xD;
                  into the study until they are asymptomatic and at least 14 days after a positive&#xD;
                  test)&#xD;
&#xD;
               2. Symptomatic congestive heart failure&#xD;
&#xD;
               3. Uncontrolled hypertension&#xD;
&#xD;
               4. Unstable angina pectoris&#xD;
&#xD;
               5. Uncontrolled cardiac arrhythmia&#xD;
&#xD;
               6. Active peptic ulcer disease or gastritis&#xD;
&#xD;
               7. Active bleeding diatheses&#xD;
&#xD;
               8. Psychiatric illness or social situations that would limit compliance with study&#xD;
                  requirements or compromise the ability of the subject to give written informed&#xD;
                  consent.&#xD;
&#xD;
         16. Active infection including&#xD;
&#xD;
               1. Tuberculosis (clinical evaluation that includes clinical history, physical&#xD;
                  examination and radiographic findings, and TB testing in line with local&#xD;
                  practice)&#xD;
&#xD;
               2. Hepatitis B (known positive HBV surface antigen (HBsAg) result). Patients with a&#xD;
                  past or resolved HBV infection (defined as the presence of hepatitis B core&#xD;
                  antibody [anti HBc] and absence of HBsAg) are eligible.&#xD;
&#xD;
               3. Hepatitis C&#xD;
&#xD;
               4. Human immunodeficiency virus (positive HIV 1/2 antibodies). Note: Patients&#xD;
                  positive for hepatitis C (HCV) antibody are eligible only if polymerase chain&#xD;
                  reaction is negative for HCV RNA.&#xD;
&#xD;
         17. Receipt of live attenuated vaccine within 30 days prior to the start of treatment.&#xD;
             Note: Patients, if enrolled, should not receive live vaccine while receiving&#xD;
             investigational medicinal product and up to 30 days after the last dose of&#xD;
             investigational medicinal product.&#xD;
&#xD;
         18. Pregnant or breastfeeding patients.&#xD;
&#xD;
         19. Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of study treatment or interpretation of patient safety or study results.&#xD;
&#xD;
         20. Known allergy or hypersensitivity to durvalumab or tremelimumab, or any of their&#xD;
             excipients.&#xD;
&#xD;
         21. Previous investigational medicinal product assignment in the present study.&#xD;
&#xD;
         22. Clinically significant pneumonitis or fibrosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James Larkin</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>RAMPART Trial Management Team</last_name>
    <phone>0044(0)207 670</phone>
    <phone_ext>4683/4743</phone_ext>
    <email>mrcctu.rampart@ucl.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Aberdeen Royal Infirmary</name>
      <address>
        <city>Aberdeen</city>
        <zip>AB25 2ZN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Gordon Urquhart</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ysbyty Gwynedd</name>
      <address>
        <city>Bangor</city>
        <zip>LL57 2PW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pasquale Innominato</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Bournemouth Hospital</name>
      <address>
        <city>Bournemouth</city>
        <zip>BH7 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Tom Geldart</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bristol Haematology and Oncology Centre</name>
      <address>
        <city>Bristol</city>
        <zip>BS2 8ED</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Amit Bahl</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Addenbrookes Hospital</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Sarah Welsh</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Centre</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jim Barber</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Broomfield Hospital</name>
      <address>
        <city>Chelmsford</city>
        <zip>CM1 7ET</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Gopalakrishnan Srinivasan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cheltenham General Hospital</name>
      <address>
        <city>Cheltenham</city>
        <zip>GL53 7AN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Marios Decatris</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Colchester General Hospital</name>
      <address>
        <city>Colchester</city>
        <zip>CO4 5JL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Muthu Kumar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Coventry &amp; Warwickshire</name>
      <address>
        <city>Coventry</city>
        <zip>CV2 2DX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Yakhub Khan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jahangeer Malik</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Balaji Venugopal</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Diana Princess of Wales Hospital</name>
      <address>
        <city>Grimsby</city>
        <zip>DN33 2BA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Iqtedar Muazzam</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Castle Hill Hospital</name>
      <address>
        <city>Hull</city>
        <zip>HU16 5JQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Anthony Maraveyas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Raigmore Hospital</name>
      <address>
        <city>Inverness</city>
        <zip>IV2 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Neil McPhail</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St James University Hospital</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Naveen Vasudev</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary</name>
      <address>
        <city>Leicester</city>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Guy Faust</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clatterbridge Cancer Centre</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7AL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Richard Griffiths</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St Bartholomew's Hospital</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Tom Powles</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mount Vernon Hospital</name>
      <address>
        <city>London</city>
        <zip>HA6 2RN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Anand Sharma</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ekaterini Boleti</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Guy's Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Sarah Rudman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>James Larkin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Charing Cross Hospital</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Naveed Sarwar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Christie</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Tom Waddell</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospital</name>
      <address>
        <city>Nottingham</city>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Poulam Patel</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Andrew Protheroe</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Glan Clwyd Hospital</name>
      <address>
        <city>Rhyl</city>
        <zip>LL18 5UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Carey MacDonald Smith</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Scunthorpe General Hospital</name>
      <address>
        <city>Scunthorpe</city>
        <zip>DN15 7BH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>George Bozas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Weston Park Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2SJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Carmel Pezaro</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>South Tyneside District Hospital</name>
      <address>
        <city>South Shields</city>
        <zip>NE34 0PL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ashraf Azzabi</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Southend University Hospital</name>
      <address>
        <city>Southend-on-Sea</city>
        <zip>SS0 0RY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Awais Jalil</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sunderland Royal Hospital</name>
      <address>
        <city>Sunderland</city>
        <zip>SR4 7TP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ashraf Azzabi</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>James Larkin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Torbay Hospital</name>
      <address>
        <city>Torquay</city>
        <zip>TQ2 7AA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Anna Lydon</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>September 3, 2020</last_update_submitted>
  <last_update_submitted_qc>September 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Renal Cell Carcinoma</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Multi-Arm Multi-Stage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03288532
org study id: MRC RE06
nct id: NCT03288532
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multi-Arm Multi-Stage Design
primary purpose: Treatment
masking: None (Open Label)
measure: Disease Free Survival (DFS): Arm C vs A
time frame: 6.25 years
description: Interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first.
measure: Disease Free Survival (DFS): Arm B vs A
time frame: 10.54 years
description: Interval from randomisation to first evidence of local recurrence, new primary RCC, distant metastases, or death from any cause, whichever occurs first.
measure: Overall Survival (OS): Arm C vs A (high risk patients only)
time frame: 13.25 years
description: All-cause mortality, the time from randomisation to death from any cause (including RCC).
measure: Overall Survival (OS): Arm B vs A (high risk patients only)
time frame: 20.5 years
description: All-cause mortality, the time from randomisation to death from any cause (including RCC).
measure: Metastasis-free survival (MFS): Arm C vs A
time frame: 6.25 years
description: Interval from randomisation to first evidence of metastases or death from RCC
measure: Metastasis-free survival (MFS): Arm B vs A
time frame: 10.54 years
description: Interval from randomisation to first evidence of metastases or death from RCC
measure: RCC specific survival time: Arm C vs A
time frame: 13.25 years
description: Time from randomisation to death from RCC
measure: RCC specific survival time: Arm C vs A
time frame: 20.5 years
description: Time from randomisation to death from RCC
arm group label: Arm A (active monitoring)
arm group type: No Intervention
description: 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
arm group label: Arm B (durvalumab monotherapy)
arm group type: Experimental
description: Participants randomised to Arm B will receive durvalumab (1500mg) 4 weekly for 1 year (13 cycles maximum)
arm group label: Arm C (durvalumab + tremelimumab)
arm group type: Experimental
description: 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)
intervention type: Drug
intervention name: Durvalumab
description: controlled infusion via an infusion pump into a peripheral or central vein
arm group label: Arm B (durvalumab monotherapy)
arm group label: Arm C (durvalumab + tremelimumab)
intervention type: Drug
intervention name: Tremelimumab
description: controlled infusion via an infusion pump into a peripheral or central vein
arm group label: Arm C (durvalumab + tremelimumab)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James Larkin
role: Principal Investigator
affiliation: Royal Marsden NHS Foundation Trust
last name: RAMPART Trial Management Team
phone: 0044(0)207 670
phone ext: 4683/4743
email: mrcctu.rampart@ucl.ac.uk
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Durvalumab
mesh term: Tremelimumab
sharing ipd: Undecided