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    Summary
    EudraCT Number:2015-000886-30
    Sponsor's Protocol Code Number:D6010C00004
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-10-03
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2015-000886-30
    A.3Full title of the trial
    A Multicentre Phase II Study of AZD1775 plus Chemotherapy in Patients with Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of AZD1775 plus Chemotherapy in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.
    A.3.2Name or abbreviated title of the trial where available
    AZD1775 + Chemotherapy to treat Ovarian, Fallopian Tube, Peritoneal Cancer.
    A.4.1Sponsor's protocol code numberD6010C00004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02272790
    A.5.4Other Identifiers
    Name:Sarah Cannon Development InnovationsNumber:GYN 49
    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 AB
    B.5.2Functional name of contact pointClinical Trial Transparancy
    B.5.3 Address:
    B.5.3.1Street AddressKarlebyhus, Astraallen
    B.5.3.2Town/ citySödertälje
    B.5.3.3Post codeSE 151 85
    B.5.3.4CountrySweden
    B.5.6E-mailClinicalTrialTransparency@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 nameAZD1775 capsule
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule, hard
    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 INNN/A
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameAZD-1775 hemihydrate; L001739996-008U
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 nameAZD1775 capsule
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule, hard
    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 INNN/A
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameAZD-1775 hemihydrate; L001739996-008U
    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: 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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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.3.4Pharmaceutical 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.3.9.3Other descriptive nameCARBOPLATIN
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration numberAUC 5 x [GFR+25]
    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 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.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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.3.4Pharmaceutical form Powder 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 INNGEMCITABINE
    D.3.9.1CAS number 95058-81-4
    D.3.9.4EV Substance CodeSUB07892MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 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.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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.3.4Pharmaceutical 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/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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 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.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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.3.4Pharmaceutical 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 INNDOXORUBICIN
    D.3.9.1CAS number 23214-92-8
    D.3.9.3Other descriptive namePegylated Liposomal Doxorubicin (PLD)
    D.3.9.4EV Substance CodeSUB06391MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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
    Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
    E.1.1.1Medical condition in easily understood language
    Ovarian and other gynecologic cancers
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this trial is to evaluate the objective response rate (ORR) of AZD1775 in combination with carboplatin, paclitaxel, gemcitabine, or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
    E.2.2Secondary objectives of the trial
    Secondary objectives:

    1. Evaluate the DoR of AZD1775 + carboplatin, paclitaxel, gemcitabine, or PLD..

    2. Evaluate the safety and tolerability of AZD1775 + carboplatin, paclitaxel, gemcitabine, or PLD in patients with platinum-resistant epithelial ovarian,fallopian tube, or primary peritoneal cancer.

    3. Evaluate DCR of AZD1775 + carboplatin, paclitaxel, gemcitabine, or PLD in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    4. Evaluate the Cancer Antigen-125 (CA-125) response of AZD1775 + carboplatin, paclitaxel, gemcitabine, or PLD in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    5. Characterise the pharmacokinetic (PK) parameters of AZD1775 + carboplatin, AZD1775 + paclitaxel, and AZD1775 + gemcitabine, and AZD1775 + PLD.

    6. Assess the drug interaction between AZD1775 + carboplatin, AZD1775 + paclitaxel, AZD1775 + gemcitabine, and AZD1775 + PLD.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Has read and understands the informed consent form (ICF) and has given written consent.

    2. Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    3. Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible.

    4. No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.

    5. Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included (applies to Arm D only).

    6. At least 1 measurable lesion according to RECIST v1.1.

    7. Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.

    8. ECOG Performance Status (PS) score of 0 - 1.

    9. Baseline Laboratory Values within 7 days of starting study drugs:
    a) ANC ≥1500/μL
    b) HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
    c) Platelets ≥ 100,000/μL
    d) ALT & AST ≤ 3 x ULN or ≤ 5 x ULN if known hepatic metastases
    e) Serum bilirubin within normal limits (WNL) or ≤1.5 x ULN in patients with liver metastases; or total bilirubin ≤ 3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert’s Syndrome.
    f) Serum creatinine ≤1.5 x ULN OR measured creatinine clearance (CrCl) ≥ 45 mL/min by the Cockcroft-Gault method.

    10. Left ventricular ejection fraction (LVEF) WNL of the institution, as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).

    11. Female patients who are not of childbearing potential and fertile female patients of
    childbearing potential who agree to use adequate contraceptive measures from 2
    weeks prior to the study and until 1 month after study treatment discontinuation,
    who are not breastfeeding, and who have a negative serum or urine pregnancy test
    within 3 days prior to start of study treatment

    12. Predicted life expectancy ≥ 12 weeks

    13. Must be ≥18 years of age.

    14. Willingness and ability to comply with study and follow-up procedures.
    E.4Principal exclusion criteria
    1. Participation in another clinical investigational study within the previous 28 days.

    2. Use of a study drug (approved or investigational drug therapy) ≤ 21 days or 5 half-lives
    (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤ 21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.

    3. Major surgical procedures ≤ 28 days of beginning study treatment, or minor surgical
    procedures ≤ 7 days. No waiting required following port-a-cath placement, or any other central venous access placement.

    4. No other chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy (except for palliative local radiotherapy), biological therapy or other novel agent is permitted while the patient is receiving study medication.

    5. Grade >1 toxicity from prior therapy (except alopecia or anorexia).

    6. Known malignant CNS disease other than neurologically stable, treated brain metastases – defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.

    7. Any prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.

    8. Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
    a) Unstable angina
    b) Congestive heart failure
    c) Acute myocardial infarction
    d) Conduction abnormality not controlled with pacemaker or medication
    e) Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).

    9. AZD1775 should not be given to patients with a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. AZD1775 has not ben studied in patients with ventricular arrhythmias or recent myocardial infarction.

    10. Corrected QT interval (QTc) >470 msec at study entry or congenital long QT syndrome. QTc interval will be calculated using Fridericia's formula (per institutional standards) obtained from 3 ECGs performed 2-5 minutes apart at study entry.

    11.Pregnant or lactating.

    12. Serious active infection upon enrolment, or other serious underlying medical condition that would impair the patient's ability to receive study treatment.

    13. Presence of other active cancers, or history of treatment for invasive cancer within the last 3 years. Patients with Stage I cancer who have received definitive local treatment within the last 3 years, and whom are considered unlikely to recur, are eligible. All patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.

    14. Psychological, familial, sociological, or geographic conditions that do not permit compliance with the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is ORR for the arms included in the efficacy assessment, defined as the proportion of patients achieving a complete or partial tumour response according to Response
    Evaluation Criteria in Solid Tumours (RECIST) v1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline, every 8 weeks (every 6 weeks for carboplatin arm only) from the first dose (every 12 weeks for patients on study > 1 year) until progression, death or until the study is terminated by the sponsor. Follow-up assessments will start 12 weeks from the date of last tumour and response assessment.
    E.5.2Secondary end point(s)
    Secondary Endpoints:

    1) DoR, defined as the time from first documented tumour response until the date of documented
    progression or death from any cause.

    2) Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and deaths; clinically significant changes in safety-related laboratory parameters according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) and abnormal vital signs.

    3) Disease Control Rate (DCR), defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.

    4) Gynaecologic Cancer Intergroup (GCIG) CA-125 response, defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥ 2 x ULN within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days.

    5) Plasma PK parameters of AZD1775 plus carboplatin, AZD1775 plus paclitaxel, and AZD1775 plus gemcitabine, and AZD1775 plus PLD.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints of Evaluation of Secondary Endpoints:

    1) Baseline, every 8 weeks (every 6 weeks for carboplatin arm) from first dose (every 12 weeks for patients on study > 1 year) until progression, death or until the study is terminated by the sponsor.

    2) Safety and tolerability is assessed from time of informed consent until the end of the study.

    3) Baseline, every 8 weeks (every 6 weeks for carboplatin arm) from first dose (every 12 weeks for patients on study > 1 year) until progression, death or until the study is terminated by the sponsor.

    4) CA-125 serum sample collected at baseline (within 14 days prior to first study treatment), Day 1 of each cycle, and end-of-study treatment visit.

    5) Blood samples are collected pre and post dose.
    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 No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    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
    Canada
    Netherlands
    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
    Last Subject Last Visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    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: 90
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 7
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12
    F.4.2.2In the whole clinical trial 97
    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)
    Treatment or care after the subject has ended participation in the trial will be no different than normal.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation No Trial Networks will be used
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-10-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-12-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-12-13
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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