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    The EU Clinical Trials Register currently displays   44132   clinical trials with a EudraCT protocol, of which   7324   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2008-002608-25
    Sponsor's Protocol Code Number:D0810C00011
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-10-03
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2008-002608-25
    A.3Full title of the trial
    A Phase I/II randomised, double-blind, multi-centre study to assess the efficacy of AZD2281 when given in combination with paclitaxel in the 1st or 2nd line treatment of patients with metastatic Triple Negative Breast Cancer
    A.4.1Sponsor's protocol code numberD0810C00011
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 support
    B.4.2Country
    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
    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 nameAZD2281 (KU-0059436)
    D.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNolaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeAZD2281 (KU-0059436
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.2.5The IMP has been designated in this indication as an orphan drug in the Community Information not present in EudraCT
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namepaclitaxel
    D.3.4Pharmaceutical form Intravenous infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive namepaclitaxel
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic Triple Negative Breast Cancer
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10055113
    E.1.2Term Breast cancer metastatic
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the Phase I part of this study is:
    · To establish the appropriate doses of paclitaxel and AZD2281 in combination, based on safety and tolerability (for use in the randomised Phase II part of the study).
    The primary objective of the Phase II part of this study is:
    · To determine the efficacy (assessed by Progression Free Survival [PFS]) of AZD2281 in combination with paclitaxel compared to paclitaxel alone in this patient population.
    E.2.2Secondary objectives of the trial
    The secondary objective of Phase I:
    · To identify any toxicities of AZD2281 in combination with paclitaxel.
    The secondary objectives of Phase II:
    · To determine the efficacy of AZD2281 in combination with paclitaxel compared to paclitaxel alone by assessment of overall survival (OS), objective response rate (ORR), duration of response, changes in Cancer Antigen (CA)-153 and Carcinoembryonic Antigen (CEA).
    · To determine the safety and tolerability of AZD2281 in combination with paclitaxel compared to paclitaxel alone.
    · To determine the effects of AZD2281 in combination with paclitaxel compared to paclitaxel alone on disease related symptoms Functional Assessment of Cancer Treatment- Breast Cancer questionnaire (FACT-B).
    · To determine the quality of life of patients treated with AZD2281 in combination with paclitaxel compared to paclitaxel alone.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of fully informed consent prior to any study specific procedures
    2. Patients must be > 18 years of age
    3. Female patients with histologically or cytologically diagnosed metastatic triple-negative breast cancer
    - Oestrogen, progesterone and HER2 negative advanced adenocarcinoma of the breast defined as:
    § For ER, PR status: Allred<3 or ER, PR IHC 0 and
    § For HER2 status: IHC 0 or 1+ or FISH negative; if IHC 2+, need negative FISH confirmation.
    4. Phase II only - At least one lesion, not irradiated within 12 weeks of the first administration of study treatment, that can be accurately measured as ³ 10 mm in the longest diameter with spiral computed tomography (CT) scan or as ³ 20 mm with conventional techniques according to RECIST (Conventional CT, MRI) and which is suitable for accurate repeated measurements.
    5. Patients must have normal organ and bone marrow function measured within 7 days prior to administration of study treatment as defined below:
    - Haemoglobin ≥ 9.0 g/dL
    - Absolute neutrophil count (ANC) ≥ 1500 x 106/L
    - White blood cells (WBC) > 3x109/L
    - Platelet count ≥ 100, 000 x 106/L
    - Total bilirubin ≤ 1.5 x institutional upper limit of normal
    - AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which it must be ≤ 5x ULN
    - Creatinine clearance (Cockcroft-Gault) within normal range (> 60 mL/min).
    - Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
    6. ECOG performance status ≤ 2 for breast (see Appendix F)
    7. Patients must have a life expectancy ≥ 16 weeks.
    8. Evidence of non-childbearing status: negative urine or serum pregnancy test within 7 days of study treatment for women of childbearing potential, or postmenopausal status
    Postmenopausal is defined by any one of the following:
    § natural menopause with last menses >1 year ago;
    § radiation-induced oophorectomy with last menses >1 year ago,
    § chemotherapy-induced menopause with >1 year interval since last menses,
    § serum follicle stimulating hormone, lutenising hormone and plasma oestradiol levels in the post menopausal range for the institution,
    § or surgical sterilisation (bilateral oophorectomy or hysterectomy).
    9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
    10. Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing. If an archived tumour sample is not available the patient will not be eligible for the study.
    For inclusion in genetic research, patients must fulfil the following criterion:
    1. Provision of informed consent for genetic research
    If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to that part.
    E.4Principal exclusion criteria
    1. Any previous treatment with a PARP inhibitor, including AZD2281, in the past or any treatment with paclitaxel within the last 12 months.'
    2. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
    3. Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to enrolment.
    4. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to enrolment.
    5. More than one prior chemotherapy for advanced disease and/or extensive irradiation leading to bone marrow deficiency. Extensive radiotherapy would be that involving 30% of the bone marrow e.g. whole pelvis or half spine.
    6. Major surgery within 4 weeks of starting the study and patients must have recovered from any effects of any major surgery.
    7. Pre-existing peripheral neuropathy > grade 1.
    8. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months), myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
    9. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication (e.g. partial bowel obstruction or malabsorption)
    10. Patients requiring treatment with inhibitors or inducers of CYP3A4 (see Section 6.4.1 for guidelines and wash out periods).
    11. Patients requiring treatment with inhibitors or inducers of CYP2C8 (see Section 6.4.2 for guidelines and wash out periods).
    12. Pregnant or breastfeeding women.
    13. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
    14. Patients with known hepatic disease (i.e., Hepatitis B or C).
    15. Persistent toxicities (grade 2 or greater) from any cause, except for alopecia
    16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
    17. Previous randomisation to treatment in the present study
    18. Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
    19. Patient with a history of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil)
    20. Patients with a known hypersensitivity to AZD2281 or any of the excipients of the product.
    21. Patients currently experiencing seizures or who were currently being treated with only anti-epileptics for seizures (use of anti-epileptic drugs to control pain is allowed in patients not suffering from seizures unless drug is excluded due to CYP3A4 induction - phenytoin, carbamazepine, phenobarbitone, see Section 6.4.1
    22. Optional pharmacogenetics sample only:
    · previous allogeneic bone marrow transplant
    · blood transfusion in the last 120 days prior to entry to the study
    E.5 End points
    E.5.1Primary end point(s)
    Phase I
    · Primary outcome variable
    - Safety: Adverse events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry, haematology and urinalysis.
    Phase II
    · Primary outcome variable
    - PFS as evaluated by RECIST
    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 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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Safety run-in
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Information not present in EudraCT
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    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 Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as when the final database lock is performedand no patients are receiving ongoing treatment with AZD2281.
    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 months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 270
    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)
    Once patients receiving AZD2281 or matching placebo have been discontinued from study treatment, other treatment options will be at the discretion of the investigator.
    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 Decision2008-12-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-11-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2009-11-09
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