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    The EU Clinical Trials Register currently displays   38003   clinical trials with a EudraCT protocol, of which   6235   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2013-002308-15
    Sponsor's Protocol Code Number:PR001
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2013-10-03
    Trial 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 number2013-002308-15
    A.3Full title of the trial
    A phase I/II dose finding study evaluating the safety and tolerability of CAPecitabine and AflIbercept in patients with unresectable metasTAtic colorectaL cancer deemed unsuitable for doublet/ triplet chemotherapy.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase I/II dose finding study evaluating the safety and tolerability of CAPecitabine and AflIbercept in patients with unresectable metasTAtic colorectaL cancer deemed unsuitable for doublet/ triplet chemotherapy.
    A.3.2Name or abbreviated title of the trial where available
    CAPITAL
    A.4.1Sponsor's protocol code numberPR001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGuys & St. Thomas' 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 supportSanofi
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGuys & St. Thomas' NHS Foundation Trust
    B.5.2Functional name of contact pointPaul Ross
    B.5.3 Address:
    B.5.3.1Street AddressOncology Department. Guys Hospital. Great Maze Pond
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSE1 9RT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number00442071884249
    B.5.5Fax number00442071883571
    B.5.6E-mailPaul.ross@gstt.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 Yes
    D.2.1.1.1Trade name Zaltrap
    D.2.1.1.2Name of the Marketing Authorisation holderSanofi Aventis Groupe
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Concentrate and solvent 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 INNAflibercept
    D.3.9.1CAS number 862111328
    D.3.9.2Current sponsor codeAVE0005
    D.3.9.3Other descriptive nameAFLIBERCEPT
    D.3.9.4EV Substance CodeSUB26987
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Xeloda
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameCapecitabine
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCAPECITABINE
    D.3.9.3Other descriptive nameCAPECITABINE
    D.3.9.4EV Substance CodeSUB12474MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number150 to 500
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Colorectal Cancer
    E.1.1.1Medical condition in easily understood language
    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 PT
    E.1.2Classification code 10061451
    E.1.2Term Colorectal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    phase 1
    To evaluate the maximum tolerated dose in a selected group of patients with good performance status with metastatic disease who have progressed on at least first line therapy.

    phase 2
    To establish safety and tolerability of recommended phase II treatment dose of aflibercept and capecitabine in patients not suitable for doublet/triplet cytotoxic chemotherapy
    E.2.2Secondary objectives of the trial
    phase 1
    To evaluate the overall treatment toxicity profile in this group.
    Overall response rate in this group

    phase 2
    To establish the overall response rate (ORR) in this group
    To assess the overall treatment utility of this combination via the use of a comprehensive health assessment tool.
    To evaluate the overall treatment toxicity profile according to the CTC v4.03.
    To assess progression free survival in this group
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Histologically confirmed colorectal cancer with evidence of metastatic disease
    Adequate medical fitness to undergo fluoropyrimidine-based chemotherapy.
    No known dihydropyrimidine dehydrogenase deficiency.
    Adequate bone marrow function with:
    platelets > 100 x 109/l; WBC > 3 x 109/l; neutrophils > 1.5 x 109/l; Hb > 9 g/dl
    Serum bilirubin < 1.5 x upper limit of institutional normal range (ULN), alkaline phosphatase < 5 x ULN and transaminases < 3 x ULN unless liver metastasis then < 5 x ULN.
    Serum creatinine ≤ 1.5 x ULN or creatinine clearance > 50ml/min
    Proteinuria < 2+ (dipstick urinalysis) or ≤ 1g/24hour.
    For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment,
    Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.
    Recovery from any treatment related grade 3/4 non-haematological toxicity (except alopecia and fatigue) to baseline or ≤ grade 1
    Absence of pre-existing liver dysfunction of Childs-Pugh B or worse
    Written informed consent
    Life expectancy > 3 months
    Age ≥ 18 years

    Phase I study specific criteria
    WHO performance status 0 – 1
    Progressive disease after at least first line chemotherapy treatment
    Previous fluoropyrimidine therapy has not required dose reduction of greater than 25%, significant delay (≥ 7 days) or stopped treatment due to fluoropyrimidine toxicity

    Phase 2 specific criteria
    WHO performance status 0 – 2
     Patients not deemed suitable for doublet/triplet combination chemotherapy.
     No previous treatment for mCRC.
    E.4Principal exclusion criteria
    Known evidence of brain metastases
    o Liver-only metastatic disease deemed to be resectable
    o LVEF <50%
    o Patients who did not previously tolerate IV 5-FU or capecitabine (required dose reduction, significant delay (≥ 7days) or stopped treatment due to fluoropyrimidine toxicity
    Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding/haemorrhage (unless due to resected tumour), treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thrombo-embolic event.
    o Any of the following within 6 months prior to inclusion: myocardial infarction, acute coronary syndrome, unstable angina pectoris, coronary revascularisation (PCI or CABG), NYHA class III or IV congestive heart failure, stroke or transient ischaemic attack.
    o Any patient who has undergone major surgery <1month prior to trial entry.
    o Uncontrolled hypertension (grade 3 /4)
    o Significant proteinuria (≥2+ on dipstick or ≥1g/24hour)
    o Significant bleeding diathesis or significant underlying coagulopathy (INR>1.5) in the absence of vitamin K antagonist therapy.
    o Intolerance to loperamide
    o Previous history of gastrointestinal fistula or perforation
    o Evidence of bowel obstruction
    o Clinically relevant history of drug or alcohol abuse
    o Serious uncontrolled inter current illness including poorly controlled diabetes mellitus
    o HIV, HBV or HCV infection.
    o Pregnancy or lactation. Men and women of child-bearing potential must use adequate contraception
    Any psychological, familial, sociological or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.
    E.5 End points
    E.5.1Primary end point(s)
    phase 1
    o To establish the maximum tolerated dose and dose-limiting toxicities in this group

    phase 2
    o Tolerability and feasbility of treatment (no dose reduction, significant treatment delay or stopping treatment early due to toxicity).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Toxicity will be assessed prior to each cycle of treatment
    E.5.2Secondary end point(s)
    phase 1
    o To evaluate the overall treatment toxicity profile in this group

    phase 2
    o Overall response rate
    o Progression free survival
    o Dose limiting toxicities.
    o Quality of life
    o Overall treatment utility via the use of comprehensive health assessment tool
    E.5.2.1Timepoint(s) of evaluation of this end point
    post study analysis
    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 No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    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 Yes
    E.8.1.7.1Other trial design description
    Dose escalation study
    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
    Dose escalation study
    E.8.2.4Number of treatment arms in the trial1
    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 concerned10
    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 trial will be closed when all participants have made their final follow-up visit, the data entered into the database and all queries resolved and the database locked.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 48
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 48
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state48
    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)
    In order to manage patient expectations in the case of a positive response to this combination of chemotherapy,
    the discretion of the PI will be exercised in terms of continuation of this treatment combination for patients. Sanofi
    Aventis will continue to provide aflibercept in such cases.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-11-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-10-11
    P. End of Trial
    P.End of Trial StatusOngoing
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