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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2017-000370-10
    Sponsor's Protocol Code Number:POLEMCCR4673
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-06-11
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-000370-10
    A.3Full title of the trial
    Avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III dMMR or POLE exonuclease domain mutant colon cancer: A phase III randomised study.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The benefit of adding drugs that stimulate the immune system to attack cancer to the standard treatment of colon cancer that has been removed surgically.
    A.3.2Name or abbreviated title of the trial where available
    POLEM
    A.4.1Sponsor's protocol code numberPOLEMCCR4673
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorThe Royal Marsden NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck Serno UK
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRoyal Marsden Hospital
    B.5.2Functional name of contact pointAngela Gillbanks
    B.5.3 Address:
    B.5.3.1Street AddressDowns Rd
    B.5.3.2Town/ citySutton,Surrey
    B.5.3.3Post codeSM2 5PT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02086426011
    B.5.6E-mailangela.gillbanks@rmh.nhs.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAvelumab
    D.3.2Product code MSB0010718C
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAvelumab
    D.3.9.1CAS number 1537032-82
    D.3.9.2Current sponsor codeMSB0010718C
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Colon cancer stage III
    E.1.1.1Medical condition in easily understood language
    Localised bowel cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10009949
    E.1.2Term Colon cancer Duke's C
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The purpose of this study is to determine if dMMR/or POLE exonuclease domain mutant stage III colon cancer patients gain clinical benefit (i.e. reduction of the risk of cancer coming back) from the PD-L1 inhibitor Avelumab in combination with standard adjuvant chemotherapy after surgical removal of the tumour.
    E.2.2Secondary objectives of the trial
    Does the combination of surgery, adjuvant chemotherapy and Avelumab increase the overall survival compared to surgery and adjuvant chemotherapy alone?

    Is the combination of surgery, adjuvant chemotherapy and Avelumab acceptable in terms of adverse events compared to surgery and adjuvant chemotherapy alone?

    Does the combination of surgery, adjuvant chemotherapy and Avelumab improve patients' quality of life compared to surgery and adjuvant chemotherapy alone?

    Is the combination of surgery, adjuvant chemotherapy and Avelumab cost-effective compared to surgery and adjuvant chemotherapy alone?
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female subjects aged ≥18 years
    2. ECOG PS 0/1
    3. Histologically proven, stage III (i.e., any T, N1 or N2, M0) adenocarcinoma of the colon (as defined by the presence of the inferior pole of the tumour above the peritoneal reflection - that is, at least 15 cm from the anal margin).
    4. Fully surgically resected tumour with clear resection margins (i.e., >1 mm)
    5. Locally confirmed defective mismatch repair (dMMR) tumour (as defined by the lack of staining on either the pre-operative biopsy samples or resection specimens of at least one of the following proteins: MLH1, MSH2, MSH6, PMS2) or centrally confirmed POLE exonuclease domain mutated tumour (in subjects <50 years old with pMMR tumours)
    6. Absence of metastases as shown by post-operative CT scan
    7. Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy
    8. Adequate hematological function defined by absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count ≥100 × 109/L, and hemoglobin ≥9 g/dL (blood transfusion before recruitment is allowed)
    9. Adequate hepatic function defined by a total bilirubin level ≤1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤2.5 × ULN
    10. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
    11. Negative serum or urine pregnancy test at screening for women of childbearing potential
    12. Fertile men and women must agree to take highly effective contraceptive precautions during, and for 6 months after the last dose of chemotherapy or for 1 month after the last dose of Avelumab
    E.4Principal exclusion criteria
    1. Rectal tumours (as defined by the presence of the inferior pole of the tumour below the peritoneal reflection - that is, <15 cm from the anal margin).
    2. Inability to start adjuvant chemotherapy within 12 weeks after surgery
    3. Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgical resection of colon cancer
    4. Prior organ transplantation, including allogeneic stem cell transplantation
    5. Significant acute or chronic infections including, among others:
    - known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    - positive test for HBV surface antigen or anti-HCV antibody and confirmatory HCV RNA test
    6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
    - Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
    - Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg/day of prednisone or equivalent
    - Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
    7. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3 NCI CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
    8. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v4.0; however, alopecia and sensory neuropathy Grade ≤2 is acceptable unless oxaliplatin administration is planned as part of the adjuvant treatment
    9. Pregnancy or lactation
    10. Known alcohol or drug abuse
    11. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
    12. Known history of colitis, pneumonitis and pulmonary fibrosis (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment.
    13. Any psychiatric condition that would prohibit the understanding or rendering of informed consent
    14. Vaccination within 4 weeks of the first dose of Avelumab and while on trial is prohibited except for administration of inactivated vaccines
    15. Other invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured. Cancer subjects with incidental histological findings of prostate cancer (tumour/node/metastasis stage of T1a or T1b or prostate-specific antigen ˂10) who have not received hormonal treatment may be included, pending a discussion with the study physician.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is DFS at 3 years.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The main analysis will take place once 60 events have occurred.
    DFS at 3 years is defined as the proportion of subjects who are alive and disease-free at 3 years. For subjects who neither progressed nor died, their DFS time will be censored at the last date of contact. Relapse will be based on RECIST (v 1.1) criteria. Where a patient has neither progressed nor died, their DFS time will be censored at the last date of contact (known to be alive and relapse free).
    E.5.2Secondary end point(s)
    • Median DFS
    • Overall survival
    • Median OS
    • Adverse events
    • HRQoL
    • Quality Adjusted Life Years (QALYs)
    • Health Resource Use
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Median DFS will be evaluated at the same time of 3-year DFS and at the end of the trial
    - Overall survival will be evaluated at 5 and 7 years
    - Median OS will be evaluated at the same time of Overall survival (see above)
    - Adverse events will be evaluated once all patients have completed treatment and at the end of the study
    - HRQoL will be evaluated at the end of the study
    - Quality Adjusted Life Years (QALYs) will be evaluated at the end of the study
    - Health Resource Use will be evaluated at the end of the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    standard adjuvant chemotherapy
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned40
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as such time as the last patient has had their last visit, or when adequate follow up has occurred for all the study end points to be assessed and reported (including overall survival which will require patients to be followed up until 7 years from the start of adjuvant chemotherapy, death or loss to follow-up), whichever is sooner.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years9
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years9
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days29
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state402
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 402
    F.4.2.2In the whole clinical trial 402
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The interventional agent will be administered for a well defined period of time (i.e., 24 weeks). For individual cases where patients are still on treatment at the time of the trial closure, the relevant pharmaceutical company will be approached to discuss the ongoing provision of drug outside of the clinical trial setting.

    Following disease progression within the trial, patients will be advised by their treating oncologist regarding any standard treatment options available to them.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-02-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-09
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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