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    Summary
    EudraCT Number:2014-001589-85
    Sponsor's Protocol Code Number:D081FC00001
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2014-08-29
    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 ConcernedGermany - BfArM
    A.2EudraCT number2014-001589-85
    A.3Full title of the trial
    A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Olaparib in gBRCA Mutated Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
    A.3.2Name or abbreviated title of the trial where available
    POLO
    A.4.1Sponsor's protocol code numberD081FC00001
    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 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 supportAstrazeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointInformation center
    B.5.3 Address:
    B.5.3.1Street AddressNot applicable
    B.5.3.2Town/ cityNot applicable
    B.5.3.3Post codeNot applicable
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.centre@astrazeneca.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 nameolaparib
    D.3.2Product code AZD2281
    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 INNolaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.3Other descriptive nameOLAPARIB
    D.3.9.4EV Substance CodeSUB32234
    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 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 nameolaparib
    D.3.2Product code AZD2281
    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 INNolaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.3Other descriptive nameOLAPARIB
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 placeboFilm-coated tablet
    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 placeboFilm-coated tablet
    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
    Patients with gBRCA mutated metastatic pancreatic cancer whose disease has not progressed on
    first line platinum based chemotherapy
    E.1.1.1Medical condition in easily understood language
    gBRCA mutated metastatic pancreatic cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the efficacy of Olaparib maintenance monotherapy compared to placebo by progression free survival (PFS)
    E.2.2Secondary objectives of the trial
    • To determine the efficacy of Olaparib maintenance monotherapy compared to placebo
    • To assess the effect of Olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC
    QLQ-C30 global QoL scale.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    For inclusion in the study patients should fulfil the following criteria:
    1. *Provision of informed consent prior to any study specific procedures
    2. *Patients must be male or female ≥18 years of age
    3. *Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
    4. Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study.
    5. Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
    6. Patients are on treatment with a first line platinum-based regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator’s opinion.
    7. Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.
    8. Patients must have normal organ and bone marrow function measured within 4 weeks prior to administration of study treatment as defined below:
    − Haemoglobin ≥ 9.0 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days
    − Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    − White blood cells (WBC) >3 x 109/L
    − No features suggestive of MDS/AML on peripheral blood smear
    − Platelet count ≥ 100 x 109/L
    − Total bilirubin ≤ 1.5 x institutional upper limit of normal
    − AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal value unless liver metastases are present in which case they must be ≤ 5x ULN
    − Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
    9. *ECOG performance status 0-1 at date signing of informed consent
    10. *Postmenopausal or evidence of non-childbearing status for women of childbearing
    potential: negative urine or serum pregnancy test. Postmenopausal is defined as:
    − Amenorrheic for 1 year or more following cessation of exogenous hormonal
    treatments
    − Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in
    the post menopausal range for women under 50
    − Radiation-induced oophorectomy with last menses >1 year ago
    − Chemotherapy-induced menopause with >1 year interval since last menses
    − Surgical sterilisation (bilateral oophorectomy or hysterectomy)
    11. *Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
    12. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary tumour or a metastatic site if available or 3 unstained cytology slides if available.
    E.4Principal exclusion criteria
    Patients should not enter the study if any of the following exclusion criteria are fulfilled:
    1. *Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or staff at the study site).
    2. gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, “Variants of uncertain clinical significance” or “Variant of unknown significance” or “Variant, favour polymorphism” or “benign polymorphism” etc.).
    3. Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.
    4. Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 2 weeks prior to study treatment.
    5. *Previous randomisation in the present study.
    6. Exposure to an investigational product within 30 days or 5 half lives (whichever is
    longer) prior to randomisation
    7. *Any previous treatment with a PARP inhibitor, including Olaparib.
    8. *Patients with second primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years prior to study entry.
    9. Resting ECG with QTc ≥ 450 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc ≥ 450 msec, patient will be eligible only if repeat ECG demonstrates QTc ≤ 450 msec.
    10. Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
    11. Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 3 peripheral neuropathy.
    12. *Patients with myelodysplastic syndrome/acute myeloid leukaemia.
    13. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
    14. *Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
    15. *Clinically significant uncontrolled medical conditions are not permitted (eg active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, recent (3 months) myocardial infarction, extensive bilateral interstitial lung disease, psychiatric illness that would limit ability to comply with study procedures, and any other medical condition that, in the opinion of the investigator, places the patient at unacceptable risk of toxicity. NB: Diabetes which
    is controlled by medication does not exclude participation in the study
    16. *Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria: Disease outside the CNS is present. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. No history of intracranial haemorrhage or spinal cord haemorrhage. Minimum of 2 weeks between completion of radiotherapy and cycle 1 Day 1 and recovery from significant (Grade ≥3) acute toxicity with no ongoing
    17. *Patients unable to swallow orally administered medication and patients with
    gastrointestinal disorders likely to interfere with absorption of the study medication.
    18. *Pregnant or breast feeding women.
    19. *Previous allogeneic bone marrow transplant.
    20. *Patients with a known hypersensitivity to Olaparib or any of the excipients of the
    product.
    21. *Whole blood transfusions in the last 120 days prior to enrolment to the study
    which may interfere with gBRCA testing (packed red blood cells and platelet
    E.5 End points
    E.5.1Primary end point(s)
    Determine the efficacy of Olaparib maintenance monotherapy compared to placebo by progression free survival (PFS)-Progression Free Survival (PFS) by BICR using modified RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    - Interim PFS analyses (~ 45 PFS events): PFS
    - Final PFS (~ 89 PFS events): PFS, PFS2, TDT, TFST, TSST, OS, time to deterioration of Global QoL and PAN-26 pain scale Efficacy Data
    - Final OS analyses (~ 106 OS events): PFS2, TFST, TSST, OS, time to deterioration of Global QoL and PAN-26 pain scale
    E.5.2Secondary end point(s)
    • To determine the efficacy of Olaparib maintenance monotherapy compared to placebo
    • To assess the effect of Olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Overall Survival (observed and predicted using observed PFS and OS data), Time from randomisation to second progression (PFS2), Time from randomisation to first subsequent therapy or death (TFST), Time from randomisation to second subsequent therapy or death (TSST), Time from randomisation to study treatment discontinuation or death (TDT), Objective Response Rate by BICR using modified RECIST 1.1 criteria for evaluable patients, Disease Control Rate at 16 weeks by BICR using modified RECIST 1.1 criteria
    - Adjusted mean change from baseline in global QoL score from the EORTC-QLQC30 questionnaire
    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) 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 Yes
    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) No
    E.8.2.2Placebo Yes
    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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Belgium
    Canada
    France
    Germany
    Israel
    Korea, Republic of
    Netherlands
    Spain
    United Kingdom
    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 last visit of the last patient undergoing the study
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months9
    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: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 75
    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 state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 61
    F.4.2.2In the whole clinical trial 145
    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)
    Patients who are receiving treatment can either choose to discontinue from the study or where the investigator believes patients are gaining clinical benefit; patients may continue to receive study treatment
    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 Decision2014-08-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-10
    P. End of Trial
    P.End of Trial StatusOngoing
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