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    The EU Clinical Trials Register currently displays   41189   clinical trials with a EudraCT protocol, of which   6743   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-005118-74
    Sponsor's Protocol Code Number:WO40181
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-04-25
    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 ConcernedGermany - BfArM
    A.2EudraCT number2017-005118-74
    A.3Full title of the trial
    A PHASE II, MULTICENTER, RANDOMIZED STUDY TO COMPARE THE EFFICACY OF VENETOCLAX PLUS FULVESTRANT VERSUS FULVESTRANT IN WOMEN WITH ESTROGEN RECEPTOR−POSITIVE, HER2−NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER WHO EXPERIENCED DISEASE RECURRENCE OR PROGRESSION DURING OR AFTER CDK4/6 INHIBITOR THERAPY
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Compare the Efficacy of Venetoclax Plus Fulvestrant Versus Fulvestrant in Women with Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer who Experienced Disease Recurrence or Progression During or after CDK4/6Inhibitor Therapy
    A.4.1Sponsor's protocol code numberWO40181
    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 SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/12/1080
    D.3 Description of the IMP
    D.3.1Product nameVenetoclax
    D.3.2Product code RO5537382
    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 INNVENETOCLAX
    D.3.9.1CAS number 1257044-40-8
    D.3.9.2Current sponsor codeRO5537382
    D.3.9.3Other descriptive nameGDC-0199, Venclexta, Venclyxto
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Faslodex
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca UK Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameFaslodex
    D.3.2Product code RO3208209
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFULVESTRANT
    D.3.9.1CAS number 129453-61-8
    D.3.9.2Current sponsor codeRO3208209
    D.3.9.3Other descriptive nameFULVESTRANT, Faslodex
    D.3.9.4EV Substance CodeSUB13933MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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
    Estrogen receptor-positive (ER+)/human epidermal growth factor receptor (HER2)-negative locally advanced or metastatic breast cancer (MBC)
    E.1.1.1Medical condition in easily understood language
    Locally advanced or metastatic breast cancer is breast cancer that has spread beyond the breast and continues to grow locally or spread to other parts of the body (metastatic)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level LLT
    E.1.2Classification code 10070575
    E.1.2Term Estrogen receptor positive breast cancer
    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
    To evaluate the efficacy of venetoclax in combination with fulvestrant compared with fulvestrant alone based on Clinical Benefit defined as
    complete response (CR), partial response (PR) or stable disease (SD)lasting ≥24 weeks from randomization in patients with measurable
    disease at baseline according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
    E.2.2Secondary objectives of the trial
    To evaluate
    - the efficacy of venetoclax in combination with fulvestrant compared with fulvestrant alone based on progression-free survival , objective response, duration of response, overall survival according to RECIST v1.1
    - Safety and tolerability of venetoclax in combination with fulvestrant compared with fulvestrant alone
    - PK of venetoclax and fulvestrant following administration of venetoclax in combination with fulvestrant
    - Predictive, prognostic, and PD biomarkers in tumor tissue and plasma associated with disease activity, response to treatment, or resistance to
    venetoclax in combination with fulvestrant
    - Patient-reported outcome (PRO)s of function, disease/treatmentrelated symptoms, GHS/overall HRQoL associated with venetoclax in combination with fulvestrant compared with fulvestrant alone
    - Compare PROs of disease-related pain in venetoclax in combination with fulvestrant compared with fulvestrant alone
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Female and >= 18 years of age

    - Histological or cytological confirmation of ER+ invasive carcinoma of the breast with documented HER2-negative as per ASCO/CAP criteria status. Patients who were originally diagnosed with HER2-positive breast cancer that converted to HER2-negative MBC are not eligible to take part in this study. Evaluable sample for B-cell lymphoma 2 (BCL-2) immunohistochemistry value at time of screening

    - Evidence of metastatic or locally advanced disease not amenable to surgical or local therapy with curative intent

    - Be either postmenopausal

    - OR pre- or perimenopausal and amenable to being treated with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin

    - Patients must not have received more than two prior lines of hormonal therapy in the locally advanced or metastatic setting. In addition, at least one line of treatment must be a CDK4/6i and patients must have experienced disease recurrence or progression during or after CDK4/6i therapy, which must have been administered for a minimum of 8 weeks prior to progression

    - Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at the time of entry into the study, as per national or local treatment guidelines

    - Women of childbearing potential must have a negative serum pregnancy test result at screening, within 14 days prior to the first study drug administration

    - For women of childbearing potential: agreement to remain abstinent or use non-hormonal contraceptive methods with a failure rate of < 1% per year during the treatment period and for up to 2 years after the last dose of study drug (or based on the local prescribing information for (fulvestrant). Women must refrain from donating eggs during this same period

    - Willing to provide tumor biopsy sample

    - Have at least one measurable lesion via RECIST v1.1

    - Have an Eastern Cooperative Oncology Group Performance Score of 0-1

    - Have adequate organ and marrow function

    - Have adequate blood coagulation

    - Have a life expectancy > 3 months
    E.4Principal exclusion criteria
    - Prior treatment with fulvestrant or other selective estrogen receptor degraders, venetoclax, or any investigational agent whose mechanism of action is to inhibit BCL-2

    - Pregnant, lactating, or intending to become pregnant during the study

    - Known untreated or active central nervous system metastases

    - Prior chemotherapy in the locally advanced or metastatic setting regardless of the duration of the treatment

    - Any anti-cancer therapy received within 21 days of the first dose of study drug, including chemotherapy, radiotherapy (except palliative intent in non-target lesion), hormonal therapy, immunotherapy, antineoplastic vaccines, or other investigational therapy

    - Concurrent radiotherapy to any site or prior radiotherapy within 21 days of Cycle 1 Day 1 or previous radiotherapy to the target lesion sites or prior radiotherapy to > 25% of bone marrow

    - Current severe, uncontrolled, systemic disease

    - Any major surgery within 28 days of the first dose of study drug or anticipation of the need for major surgery during the course of study treatment

    - Administration of the following agents within 7 days prior to the first dose of study drug: - Steroid therapy for anti-neoplastic intent, - Strong CYP3A inhibitors or moderate CYP3A inhibitors, - Strong CYP3A inducers or moderate CYP3A inducers

    - Consumption of one or more of the following within 3 days prior to the first dose of study drug: Grapefruit or grapefruit products; Seville oranges including marmalade containing Seville oranges; Star fruit (carambola)

    - Need for current chronic corticosteroid therapy

    - Known infection with HIV or human T-cell leukemia virus 1

    - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1 Day 1

    - Positive test results for hepatitis B core antibody (HBcAb) or hepatitis C virus (HCV) antibody at screening

    - Active HCV infection, defined as having a positive HCV antibody test at screening

    - History of other malignancies within the past 5 years except for treated skin basal cell carcinoma, squamous cell carcinoma, non-malignant melanoma <= 1.0 mm without ulceration, localized thyroid cancer, or cervical carcinoma in-situ

    - Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study

    - Cardiopulmonary dysfunction

    - Other medical or psychiatric conditions that, in the opinion of the investigatory, may interfere with the patient’s participation in the study

    - Inability or unwillingness to swallow pills or receive intra muscular injections

    - History of malabsorption syndrome or other condition that would interfere with enteral absorption

    - History of inflammatory bowel disease or active bowel inflammation

    - Concurrent hormone replacement therapy

    - Inability to comply with study and follow-up procedures

    - Known hypersensitivity to any of the study medications or to any of the excipients
    E.5 End points
    E.5.1Primary end point(s)
    1. Clinical benefit defined as CR, PR or SD lasting ≥24 weeks
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to 2 years after the last patient is enrolled or all patients in the study have withdrawn consent or died, or if the study is prematurely
    terminated by the Sponsor, whichever occurs first (approximately 43 months)
    E.5.2Secondary end point(s)
    1. Progression-free survival
    2. Objective response
    3. Duration of response
    4. Overall survival
    5. Frequency and severity of adverse events, focusing on serious adverse events (SAEs), adverse events of special interest (AESI), and AEs leading to drug and/or study discontinuation
    6. Plasma concentrations of venetoclax and fulvestrant and fulvestrant at specified timepoints
    7. Plasma concentrations or PK parameters of venetoclax and fulvestrant given in combination compared with these agents given alone
    8. Baseline BCL 2 protein levels as measured by IHC correlating with clinical response measures
    9. Expanded biomarkers measured at baseline, on-treatment, and at end of treatment relative to clinical response measures
    10. Mean and mean changes from baseline scores in functional (i.e., role, physical, emotional, and social), disease/treatment-related symptoms, and GHS/HRQoL by cycle as assessed by the scales of the EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C
    30
    11. Change in baseline pain score as assessed by the pain scale of EORTC QLQ-C30
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-5. Up to 2 years after the last patient is enrolled or all patients in the
    study have withdrawn consent or died, or if the study is prematurely terminated by the Sponsor,
    whichever occurs first (approximately 43 months)
    6-7. Day 1 of Cycle 1, 2, 6 and at study drug discontinuation/early termination
    8-9. Mandatory: at baseline (day-28—1), Optional at: Day 1 of Cycle 3, 4 and at study drug discontinuation visit
    10-11. At baseline, Day 1 of each cycle and at study drug discontinuation visit
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    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 Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    France
    Germany
    United Kingdom
    United States
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial 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: 105
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    ESTROGEN RECEPTOR−POSITIVE, HER2−NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER
    F.4 Planned number of subjects to be included
    F.4.1In the member state19
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 105
    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)
    An eligible patient will receive free of charge venetoclax after completing the study under the following conditions, and in accordance to Roche Global Policy on Continued Access to IMP:
    · The patient has a life-threatening or severe medical condition and requires continued Roche IMP treatment
    · There are no appropriate alternative treatments available
    · The patient and his or her doctor comply with and satisfy any legal or regulatory requirements that apply to them
    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 Decision2018-10-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-01-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-05-05
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