Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2014-003319-12
    Sponsor's Protocol Code Number:ICR-CTSU-2014-10046
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-02-04
    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 number2014-003319-12
    A.3Full title of the trial
    Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)
    A.3.2Name or abbreviated title of the trial where available
    RIO - Rucaparib Window of Opportunity Study
    A.4.1Sponsor's protocol code numberICR-CTSU-2014-10046
    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 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 supportClovis Oncology Inc.
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportCancer Research UK - Endorsement
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    B.Sponsor: 2
    B.1.1Name of SponsorThe Insitute of Cancer Research
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationThe Institute of Cancer Research
    B.5.2Functional name of contact pointChristy Toms
    B.5.3 Address:
    B.5.3.1Street AddressICR-CTSU, 15 Cotswold Road
    B.5.3.2Town/ citySutton
    B.5.3.3Post codeSM2 5NG
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02087224266
    B.5.6E-mailrio-icrctsu@icr.ac.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 nameRucaparib (camphorsulfonic acid salt form)
    D.3.2Product code CO-338
    D.3.4Pharmaceutical form 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 INNRucaparib
    D.3.9.1CAS number 283173-50-2
    D.3.9.2Current sponsor code459868-92-9
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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
    Primary breast cancer
    E.1.1.1Medical condition in easily understood language
    Primary breast cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10057654
    E.1.2Term Breast cancer female
    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
    The main aim of this study is to determine the proportion of triple negative breast cancers (TNBCs) that respond to 12-14 days treatment with the PARP inhibitor rucaparib. The cell proliferation marker Ki67 will be used to measure treatment response.

    Ki67 has been widely used to measure proliferation in human breast cancer. Preclinical studies have shown that Ki67 levels decrease in response to PARP inhibition in xenografts of an HR deficient cancer cell line and that the degree of suppression of Ki67 is also associated with the magnitude of xenograft response to PARP inhibition in vivo.

    The exploratory analysis of Ki67 in BRCA1 and BRCA2 germline mutation carriers will be used to assess the validity of fall in Ki67 as a surrogate for sensitivity to rucaparib. From prior work it is anticipated that a majority of untreated BRCA1 and BRCA2 related cancers should show a fall in Ki67 on rucaparib.
    E.2.2Secondary objectives of the trial
    - To identify a subgroup of TNBCs that are sensitive to rucaparib using baseline biomarkers of BRCA1 gene methylation and a genomic predictor of homologous recombination (HR) deficiency (DNA repair pathway).
    - To determine the proportion of TNBC cells undergoing apoptosis (cell death) following 12-14 days treatment with rucaparib.
    - To establish the proportion of TNBCs that display evidence of a defect in HR-based DNA repair as determined by the number of cells that fail to induce RAD51 foci, a cellular indicator of DNA repair.
    - To determine the extent rucaparib inhibits PARP in TNBC cells following 12-14 days rucaparib treatment.
    - To establish the safety of rucaparib treatment and how well this is tolerated in patients.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or female patients aged 16 years or older
    • Histologically proven carcinoma of the breast amenable to biopsy
    • Either breast tumour size 1.5cm or greater OR <1.5cm tumour with cytologically or histologically confirmed axillary lymph node metastases
    • WHO performance status 0, 1 or 2
    • Either
    Primary sporadic triple negative breast cancer defined as oestrogen receptor (ER) negative, progesterone receptor (PgR) negative (where available) (as defined by Allred score 0/8 or 2/8 or stain in <1% of cancer cells) and HER2 negative (immunohistochemistry 0/1+ or negative in situ hybridization) as determined by local laboratory. Patients should not be known to have a germline pathogenic BRCA1 or BRCA2 mutation at study entry.
    OR
    Primary BRCA1/2 related breast cancer as defined by a breast carcinoma of any phenotype (ER +ve/–ve, PgR +ve/–ve or unknown, HER2 +ve/–ve) occurring in a patient with a known germline pathogenic BRCA1 or BRCA2 mutation
    • Adequate organ function confirmed by the following laboratory values obtained within 14 days prior to trial entry.
    bone marrow function: neutrophils ≥ 1.5 x 109/L; Platelets >100×109/L; Hemoglobin ≥9 g/dL
    hepatic function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); Bilirubin ≤1.5 x ULN
    renal function: serum creatinine ≤1.5 x ULN
    • Patients or patients with partners of childbearing potential must use adequate contraception during trial participation. A negative pregnancy test is required by female patients 72 hours prior to trial entry. Female patients will be deemed not of childbearing potential if they are postmenopausal (aged >50 and amenorrhoeic for at least 12 months) or have had irreversible surgical sterilization
    • ER negative patients may enter the trial whether or not they have taken hormone replacement therapy (HRT) or the oral contraceptive pill (OCP) within the last four weeks. ER positive patients on HRT or the OCP must either continue HRT/OCP for the duration of the study or must not have taken HRT/OCP within the last four weeks before trial entry. The possible benefits and risks of continuing HRT/OCP must be discussed with the patient
    • Patients with primary breast cancer and evidence of metastatic disease on first presentation are eligible providing they have not had prior treatment
    • Patients must be willing and able to provide informed consent and to comply with all study procedures (including providing additional tumour biopsies for research purposes) and visit schedules
    E.4Principal exclusion criteria
    • Any prior or concurrent treatment for the current diagnosis of breast cancer.
    • Any anti-cancer treatment within the previous 12 months for prior diagnosis of cancer other than for basal cell carcinoma of the skin or cervical carcinoma in situ.
    • Prior history of ipsilateral breast cancer within the previous 5 years.
    • Impaired cardiac function or clinically significant cardiac disease, including any of the following:
    o unstable angina pectoris ≤3 months prior to first scheduled dose of rucaparib
    o acute myocardial infarction ≤3 months prior to first scheduled dose of rucaparib
    • Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent.
    • Treatment with an unlicensed or investigational drug within 4 weeks prior to trial entry.
    • Prior treatment with any PARP inhibitor, including oral or intravenous rucaparib.
    • Administration of strong CYP1A2 and CYP3A4 inhibitors or inducers (as detailed in Appendix 1) ≤7 days prior to first scheduled dose of rucaparib.
    • Females who are pregnant or breastfeeding.
    E.5 End points
    E.5.1Primary end point(s)
    The cell proliferation marker Ki67 will be used to measure treatment response. Response to rucaparib is defined as 50% or greater fall in Ki67 from baseline.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Ki67 levels will be assessed in tumour tissue biopsied at baseline (day 0) and on the last day of rucaparib treatment (day 12-14)
    E.5.2Secondary end point(s)
    Safety and tolerability will be assessed in all patients. All other secondary endpoints will be performed on patients with sporadic triple negative breast cancer only.

    • Association between baseline biomarkers of BRCA1 methylation, a genomic predictor of HR deficiency, and a drop in Ki67.
    • Apoptosis induction following 12-14 days of rucaparib treatment in patients with sporadic triple negative cancers.
    • Association between sporadic TNBC and evidence of a defect in HR based DNA repair, assessed as the proportion of sporadic TNBC that fail to induce RAD51 foci.
    • Safety and tolerability of rucaparib
    • Association of biomarkers with RAD51 score on day 12-14 biopsy
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety and tolerability will be assessed in patients at day 8, day 12-14, 28 days after end of rucaparib treatment and a final assessment post surgery.

    All other evaluations will occur in samples taken at baseline (blood and tissue)and after 12-14 days of rucaparib treatment (tissue).
    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 Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 concerned11
    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 Yes
    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 date of last data capture.
    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 days1
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 3
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 35
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 53
    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 state91
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 91
    F.4.2.2In the whole clinical trial 91
    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)
    There will be no arrangements for patients to continue to receive rucaparib once the research has finished. Rucaparib is not currently licenced. Patients will continue to receive standard care as deemed appropriate by their treating clinician.
    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 Decision2015-03-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-01-30
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-04-23
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 07:49:39 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA