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    Summary
    EudraCT Number:2011-002913-12
    Sponsor's Protocol Code Number:M12-895
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2012-01-05
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2011-002913-12
    A.3Full title of the trial
    A Randomized, Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination with Temozolomide or Veliparib in Combination with Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects with BRCA1 or BRCA2 Mutation and Metastatic Breast Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of
    (a) Veliparib and Temozolomide or
    (b) Veliparib, Carboplatin and Paclitaxel or
    (c) Placebo, Carboplatin and Paclitaxel
    in patients with Breast Cancer
    A.4.1Sponsor's protocol code numberM12-895
    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 SponsorAbbVie Deutschland GmbH & Co. KG
    B.1.3.4CountryGermany
    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 supportAbbVie Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAbbVie Ltd.
    B.5.2Functional name of contact pointEU Clinical Trials Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressAbbott House, Vanwall Business Park, Vanwall
    B.5.3.2Town/ cityMaidenhead, Berkshire
    B.5.3.3Post codeSL6 4XE
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 (0) 1628 644475
    B.5.5Fax number+44 (0) 1628 644330
    B.5.6E-maileu-clinical-trials@abbvie.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVeliparib 10 mg
    D.3.2Product code ABT-888
    D.3.4Pharmaceutical form Capsule
    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 INNVeliparib
    D.3.9.2Current sponsor codeABT-888
    D.3.9.3Other descriptive name1H-Benzimidazole-7-carboxamide, 2-[(2R)-2-methyl-2-pyrrolidinyl]-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 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 nameVeliparib 20 mg
    D.3.2Product code ABT-888
    D.3.4Pharmaceutical form Capsule
    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 INNVeliparib
    D.3.9.2Current sponsor codeABT-888
    D.3.9.3Other descriptive name1H-Benzimidazole-7-carboxamide, 2-[(2R)-2-methyl-2-pyrrolidinyl]-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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.IMP: 3
    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 nameVeliparib 40 mg
    D.3.2Product code ABT-888
    D.3.4Pharmaceutical form Capsule
    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 INNVeliparib
    D.3.9.2Current sponsor codeABT-888
    D.3.9.3Other descriptive name1H-Benzimidazole-7-carboxamide, 2-[(2R)-2-methyl-2-pyrrolidinyl]-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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: 4
    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.2.5The 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 nameTemozolomide 5 mg
    D.3.2Product code TMZ
    D.3.4Pharmaceutical form Capsule
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.3Other descriptive nameTMZ
    D.3.9.4EV Substance CodeSUB10889MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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: 5
    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.2.5The 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 nameTemozolomide 20 mg
    D.3.2Product code TMZ
    D.3.4Pharmaceutical form Capsule
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.3Other descriptive nameTMZ
    D.3.9.4EV Substance CodeSUB10889MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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.IMP: 6
    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.2.5The 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 nameTemozolomide 100 mg
    D.3.2Product code TMZ
    D.3.4Pharmaceutical form Capsule
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.3Other descriptive nameTMZ
    D.3.9.4EV Substance CodeSUB10889MIG
    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: 7
    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.2.5The 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 nameCarboplatin 10 mg/ml concentrate for solution for infusion
    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 INNCARBOPLATIN
    D.3.9.1CAS number 41575-94-4
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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: 8
    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.2.5The 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 namePaclitaxel
    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 INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    BRCA1 or BRCA2 mutation metastatic breast cancer
    E.1.1.1Medical condition in easily understood language
    BRCA1 or BRCA2 mutation metastatic 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 14.1
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic 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 assess the progression-free survival of oral veliparib in combination with temozolomide or in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in subjects with BRCA1 or BRCA2 mutation and locally recurrent or metastatic breast cancer.
    E.2.2Secondary objectives of the trial
    To assess overall survival, clinical benefit rate & objective response rate in those subjects treated with veliparib plus TMZ or treated with veliparib plus carboplatin and paclitaxel versus placebo plus carboplatin and paclitaxel.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. ≥ 18 years of age.
    2. Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic. Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
    3. Must have a documented deleterious BRCA1 or BRCA2 germline mutation. The investigator should ensure that the testing is consistent with local guidelines, and clinical practice, and that the
    test uses either 1) direct DNA sequencing/multiplex ligation-dependent probe amplification (MLPA) or 2) a well-characterized methodology previously validated by sequencing, such as that
    used to assess founder mutations. If testing has been performed by a laboratory other than Sponsor core laboratory, subjects may be enrolled but must be re-tested by Sponsor core laboratory for
    confirmation of BRCA1 or BRCA2 germline mutations.
    4. If HER2 positive (HER2 3+ by immunohistochemistry or amplification by fluorescence in situ hybridization [FISH > 2]), subjects must have received and progressed on at least one prior
    standard HER2-directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
    5. Measurable or non-measurable (but radiologically evaluable disease per RECIST version 1.1 on computed tomography (CT) scan (within 28 days of C1D1) with at least one lesion outside previously irradiated areas.
    6. ECOG Performance status of 0 to 2 (within 28 days of C1D1).
    7. Adequate hematologic, renal, and hepatic function as detailed in the protocol.
    8. Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and for 90 days
    following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation. To be considered of non-child bearing potential, postmenopausal women must be amenorrheic for at least 12 months or subjects must be surgically sterile.
    - Total abstinence from sexual intercourse (for a minimum of one complete menstrual cycle prior to study drug administration);
    - Vasectomized male subjects or vasectomized partner of female subjects;
    - Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream);
    - Intra-Uterine Device (IUD);
    - Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion of therapy.
    9. Capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to initiation of any screening or study-specific procedures.
    E.4Principal exclusion criteria
    1. Received anticancer agent(s) or an investigational agent within 21days prior to C1D1 or radiotherapy within 28 days prior to C1D1. Prior treatment with palliative local breast or bone lesion radiation (other than pelvis) can occur, if administered at least 14 days prior to C1D1. Subjects experiencing a significant adverse effect or toxicity (Grade 3 or Grade 4), causally attributed to previous anticancer treatment that has not recovered to at least Grade 2 are excluded. Anticancer hormonal therapy must be stopped 7 days before starting C1D1. Subjects receiving bisphosphonates or denosumab are eligible.
    2. More than 2 prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease.
    - Regimens received in the adjuvant/neoadjuvant setting or for locally recurrent breast cancer within the past 6 months will also be considered toward the maximum of 2 prior lines of therapy.
    - A regimen will be considered a line of therapy if it includes a cytotoxic agent administered for the treatment of breast cancer more than 1 full cycle. Therapy administered for 1 full cycle or less will not be counted towards the number of lines of therapy unless the patient experienced progression of disease while on that therapy.
    - Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., trastuzumab lapatinib, erlotinib, gefitinib, bevacizumab) are allowed and are not counted towards the prior line of therapy.
    3. Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly-(ADP-ribose)-Polymerase (PARP)-inhibitor.
    - Therapy with temozolomide, a platinum agent, or a PARP inhibitor administered for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy.
    4. Prior taxane therapy administered for the treatment of metastatic breast cancer disease with the below exceptions.
    - Prior taxane therapy for metastatic breast cancer is allowed if the patient received ≤ 1 full cycle (i.e., within 4 weeks for subjects receiving weekly paclitaxel or Abraxane; within 3 weeks for subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of progression or if taxane therapy for metastatic disease was > 12 months prior to C1D1.
    - Use of taxanes as adjuvant therapy or to treat locally recurrent disease is permitted, if given more than 6 months prior to C1D1.
    In all cases, the subject must be an appropriate candidate for paclitaxel therapy as per standard practice and per the investigator's discretion.
    5. A history of or evidence of brain metastases or leptomeningeal disease. Subjects with symptoms to suggest central nervous system (CNS) metastases should have a brain MRI within 28 days of enrollment to confirm the absence of CNS metastases. Contrast CT is acceptable for subjects who are unable to undergo a brain MRI.
    6. A history of uncontrolled seizure disorder.
    7. Pre-existing neuropathy from any cause in excess of Grade 1.
    8. Known history of allergic reactions to cremophor-paclitaxel.
    9. Clinically significant uncontrolled condition(s).
    - Active infection;
    - Symptomatic congestive heart failure;
    - Unstable angina pectoris or cardiac arrhythmia;
    - Myocardial infarction within last 6 months;
    - Psychiatric illness/social situations that would limit compliance with study requirements;
    or
    - Any medical condition which in the opinion of the investigator places the subject at an unacceptably high risk for toxicities.
    10. A previous or concurrent cancer that is distinct in primary site or histology from metastatic breast cancer, except cervical carcinoma in situ, non-melanoma carcinoma of the skin, or in situ
    carcinoma of the bladder. Any cancer curatively treated greater than 3 years prior to entry is permitted. For these subjects, metastases must be histologically or cytologically confirmed to be
    breast cancer.
    11. Pregnant or breastfeeding.
    E.5 End points
    E.5.1Primary end point(s)
    Progression Free Survival
    E.5.1.1Timepoint(s) of evaluation of this end point
    Progression Free Survival is defined as the number of days from the date the subject was randomized to the date the subject experienced a confirmed event of disease progression (as determined by the central imaging center), or to the date of death (all causes of mortality), if disease progression is not reached.
    E.5.2Secondary end point(s)
    Overall Survival, Clinical Benefit Rate and Objective Response Rate
    E.5.2.1Timepoint(s) of evaluation of this end point
    Overall Survival - number of days from randomization to date of death.

    Clinical Benefit Rate - number of subjects who have at least stable disease or Non-CR/Non-PD through the end of Week 18. All intent to treat subjects will be included in the analysis.

    Objective Response Rate - all subjects who have had at least one measurable lesion at baseline will be included in the objective response rate calculation

    Chemotherapy-Induced Peripheral Neuropathy - scores from the EORTC QLQ-CIPN20 instrument will be evaluated per published literature. In addition, the incidence of treatment-emergent Grade 3 or 4 adverse events of peripheral neuropathy will be obtained.
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    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 Yes
    E.8.1.7.1Other trial design description
    Partially blinded
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    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
    Argentina
    Australia
    Brazil
    Canada
    Czech Republic
    Denmark
    Finland
    France
    Hungary
    Israel
    Norway
    Poland
    Russian Federation
    Slovakia
    Ukraine
    United States
    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 end-of-study is defined as the date of the last subject's last visit, or last follow-up visit, which is longer.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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: 210
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 85
    F.4.2.2In the whole clinical trial 255
    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)
    Upon completion of the study, the subjects will be treated in accordance with the Investigator's best clinical judgement.
    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 Decision2012-02-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-02-21
    P. End of Trial
    P.End of Trial StatusOngoing
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