Clincosm LogoSign in Get a demo

Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02272790
Collaborator
(none)
95
Enrollment
20
Locations
4
Arms
94.9
Anticipated Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is an open-label, four-arm lead-in safety and efficacy study in which adavosertib will be combined in four separate treatment arms as follows: adavosertib plus gemcitabine (Arm A); adavosertib plus weekly paclitaxel (Arm B); adavosertib plus carboplatin (Arm C); and adavosertib plus PLD (Arm D). A subset of patients will be evaluated for the safety assessment of each treatment arm.

The adavosertib plus paclitaxel arm (Arm B) will enrol approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.

In addition, the adavosertib plus carboplatin arm (Arm C) will enrol approximately 23 patients overall at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.

To further optimise the dosing schedule of adavosertib in Arm C, a safety expansion arm (referred to as Arm C2) of approximately 12 additional patients will be enrolled at selected sites to explore emerging pre-clinical and clinical data that suggest that prolonged adavosertib exposure may increase the clinical activity.

Study Design

Study Type:
Interventional
Actual Enrollment :
95 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Actual Study Start Date :
Jan 30, 2015
Actual Primary Completion Date :
Dec 13, 2018
Anticipated Study Completion Date :
Dec 27, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (adavosertib + gemcitabine)

Adavosertib (175 mg PO) will be taken on Days 1-2, 8-9, and 15-16. Gemcitabine 800 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle.

Drug: Adavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
Other Names:
  • MK1775

    • Drug: Gemcitabine
    Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.
    Experimental: Arm B (adavosertib + paclitaxel)

    Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days weekly (Days 1-3, 8-10, and 15-17). Weekly paclitaxel 80 mg/m² IV will be administered according to institutional standards on Day 1, 8, and 15 of each 28 day cycle.

    Drug: Adavosertib
    Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
    Other Names:
  • MK1775

    • Drug: Paclitaxel
    Paclitaxel will be administered as a 1-hour IV infusion (± 10 minutes) at a dose of 80 mg/m2 according to institutional standards on Days 1, 8, and 15 of each 28 Day cycle. Patients should be pre-medicated with corticosteroids, diphenhydramine and/or H2 antagonists according to institutional standards.
    Other Names:
  • Taxol

    		•
    Experimental: Arm C/C2 (adavosertib + carboplatin)

    Arm C: Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days (Days 1-3). Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21-Day cycle. Arm C2: Five doses of adavosertib (225 mg PO BID) 2.5 days per dosing week (QW), on Weeks 1 (D1-3), 2 (D8-10) and 3 (D15-17), or on Weeks 1 (D1-3) and 2 (D8-10) ( 2 weeks on followed by 1 week off.) Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21 day cycle.

    Drug: Adavosertib
    Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
    Other Names:
  • MK1775

    • Drug: Carboplatin
    Carboplatin, at a dose calculated to produce an AUC of 5 will be administered by intravenous infusion according to institutional standards on Day 1 of each 21 Day cycle. The carboplatin dose will be calculated using the Calvert Formula based on the patient's glomerular filtration rate (GFR) which is estimated by using the creatinine clearance.
    Other Names:
  • Paraplatin

    		•
    Experimental: Arm D (adavosertib + PLD)

    Five doses of adavosertib (175 mg or 225 mg) will be taken in approximate 12 hour intervals over 2.5 days (Days 1, 2, and 3) of each 28-day cycle. PLD will administered IV on Day 1 of each cycle.

    Drug: Adavosertib
    Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
    Other Names:
  • MK1775

    • Drug: PLD
    PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) [Throughout the duration of the study (up to 19 months)]

      Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.

    Secondary Outcome Measures

    1. Disease Control Rate (DCR) [Throughout the duration of the study (up to 19 months)]

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

    2. Duration of Response (DoR) [Throughout the duration of the study, approximately 19 months.]

      Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause.

    3. Progression Free Survival (Median, 80% CI) [Throughout the Study, Approximately 4 years]

      Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates.

    4. Progression Free Survival (Median, 95% CI) [Throughout the Study, Approximately 4 years]

      Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates.

    5. Overall Survival (Median, 80% CI) [Throughout the Study, Approximately 4 years]

      Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.

    6. Overall Survival (Median, 95% CI) [Throughout the Study, Approximately 4 years]

      Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.

    7. Gynecologic Cancer Intergroup (GCIG) CA-125 Response [Throughout the study, approximately 4 years]

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

    8. The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal

    9. The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade [Throughout the duration of the study (up to 19 months)]

      The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal

    10. The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal

    11. Serious Adverse Events [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one serious adverse event (SAE).

    12. Serious Adverse Events Leading to Death [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one serious adverse event (SAE) leading to death.

    13. Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.

    14. Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.

    15. Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.

    16. Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.

    17. Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.

    18. Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption [Throughout the duration of the study (up to 19 months)]

      The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.

    19. Single Dose Adavosertib Cmax [Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr]

      Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.

    20. Multiple Dose Adavosertib Cmax [Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr]

      Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.

    21. Single Dose Adavosertib Tmax [Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr]

      The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.

    22. Multiple Dose Adavosertib Tmax [Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr]

      The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No

    Inclusion

    • Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures.

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

    • 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.

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

    • 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.

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

    • 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.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1.

    • Baseline Laboratory Values:

    1. ANC ≥1500/μL

    2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days

    3. Platelets ≥ 100,000/μL

    4. ALT & AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases

    5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the 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.

    6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.

    • 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).

    • Female patients, ≥18, (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 72 hours prior to start.

    • Predicted life expectancy ≥ 12 weeks

    Exclusion

    • 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.

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

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

    • 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.

    • Patient has had 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 last dose of study drug.

    • Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib.

    • Herbal medications should be discontinued 7 days prior to the first dose of study treatment.

    • Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:

    1. Unstable angina pectoris

    2. Congestive heart failure

    3. Acute myocardial infarction

    4. Conduction abnormality not controlled with pacemaker or medication

    5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).

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

    • Corrected QT interval (QTc) >470 msec at study entry or congenital long QT syndrome.

    • Pregnant or lactating.

    • Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment.

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Gilbert Arizona United States 85234
    2 Research Site Tucson Arizona United States 85724
    3 Research Site La Jolla California United States 92093
    4 Research Site Los Angeles California United States 90024
    5 Research Site San Francisco California United States 94158
    6 Research Site Tampa Florida United States 33612
    7 Research Site West Palm Beach Florida United States 33401
    8 Research Site Augusta Georgia United States 30912
    9 Research Site Boston Massachusetts United States 02215
    10 Research Site Detroit Michigan United States 48201
    11 Research Site New York New York United States 10019
    12 Research Site New York New York United States 10065
    13 Research Site Cleveland Ohio United States 44195
    14 Research Site Oklahoma City Oklahoma United States 73104
    15 Research Site Abington Pennsylvania United States 19001
    16 Research Site Nashville Tennessee United States 37203
    17 Research Site Dallas Texas United States 75390
    18 Research Site Milwaukee Wisconsin United States 53226
    19 Research Site Toronto Ontario Canada M5G 2M9
    20 Research Site Amsterdam Netherlands 1066 CX

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Kathleen Moore, MD, Stephenson Cancer Center, University of Oklahoma Health Sciences Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02272790
    Other Study ID Numbers:
    • D6010C00004
    • GYN 49
    First Posted:
    Oct 23, 2014
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
    Additional relevant MeSH terms:
    Peritoneal Neoplasms
    Gemcitabine
    Paclitaxel
    Carboplatin
    Adavosertib

    Study Results

    Participant Flow

    Recruitment Details This multi-center study was conducted at 20 sites: 18 in the USA, 1 in Canada, and 1 in The Netherlands. Ninety-five (95) patients were enrolled; 94 patients received treatment. The first patient started treatment on 2 Feb 2015; the final patients were still receiving treatment and were censored at the time of database lock on 14 Dec 2018.
    Pre-assignment Detail One hundred twenty-six (126) patients consented and underwent screening; 94 patients passed screening, whereas 32 patients failed screening tests and were not eligible. The Full Analysis Set consists of 94 patients.
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Period Title: Overall Study
    STARTED 9 39 23 12 6 6
    COMPLETED 9 38 23 12 6 6
    NOT COMPLETED 0 1 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg Total
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Total of all reporting groups
    Overall Participants 9 38 23 12 6 6 94
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.6
    (9.75)
    60.9
    (8.16)
    62.1
    (11.29)
    60.3
    (6.96)
    57.3
    (14.58)
    61.0
    (7.16)
    60.7
    (9.30)
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    63.0
    60.0
    62.0
    58.5
    58.5
    60.5
    60.0
    Sex: Female, Male (Count of Participants)
    Female
    9
    100%
    38
    100%
    23
    100%
    12
    100%
    6
    100%
    6
    100%
    94
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    11.1%
    6
    15.8%
    2
    8.7%
    2
    16.7%
    0
    0%
    1
    16.7%
    12
    12.8%
    Not Hispanic or Latino
    8
    88.9%
    31
    81.6%
    21
    91.3%
    10
    83.3%
    5
    83.3%
    5
    83.3%
    80
    85.1%
    Unknown or Not Reported
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    2
    2.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    5
    13.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    5.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    22.2%
    4
    10.5%
    2
    8.7%
    0
    0%
    0
    0%
    0
    0%
    8
    8.5%
    White
    7
    77.8%
    24
    63.2%
    20
    87%
    10
    83.3%
    6
    100%
    6
    100%
    73
    77.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    5
    13.2%
    1
    4.3%
    2
    16.7%
    0
    0%
    0
    0%
    8
    8.5%
    Region of Enrollment (Number) [Number]
    United States
    7
    77.8%
    30
    78.9%
    23
    100%
    12
    100%
    6
    100%
    6
    100%
    84
    89.4%
    Canada
    2
    22.2%
    7
    18.4%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    9.6%
    Netherlands
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Age (Count of Participants)
    < 65
    5
    55.6%
    26
    68.4%
    14
    60.9%
    8
    66.7%
    3
    50%
    3
    50%
    59
    62.8%
    ≥ 65
    4
    44.4%
    12
    31.6%
    9
    39.1%
    4
    33.3%
    3
    50%
    3
    50%
    35
    37.2%
    ECOG Performance Status (Count of Participants)
    PS = 0
    5
    55.6%
    19
    50%
    13
    56.5%
    4
    33.3%
    1
    16.7%
    3
    50%
    45
    47.9%
    PS = 1
    4
    44.4%
    19
    50%
    10
    43.5%
    8
    66.7%
    5
    83.3%
    3
    50%
    49
    52.1%
    PS = 2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    PS = 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    PS = 4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Time from 1st positive biopsy for disease to consent for this study (mean) (Weeks) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Weeks]
    52.0
    (11.83)
    70.9
    (46.42)
    62.3
    (24.68)
    86.1
    (55.67)
    61.4
    (23.88)
    65.8
    (20.82)
    68.0
    (38.93)
    Time from 1st positive biopsy for disease to consent for this study (median) (Days) [Median (Full Range) ]
    Median (Full Range) [Days]
    49.9
    54.9
    54.1
    74.9
    62.9
    71.1
    54.9
    Local or Regional Recurrence (Count of Participants)
    Yes
    5
    55.6%
    26
    68.4%
    17
    73.9%
    9
    75%
    4
    66.7%
    6
    100%
    67
    71.3%
    No
    4
    44.4%
    12
    31.6%
    6
    26.1%
    3
    25%
    2
    33.3%
    0
    0%
    27
    28.7%
    Time from local/regional recurrence to consent for this study (mean) (Weeks) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Weeks]
    12.2
    (14.98)
    34.3
    (51.20)
    20.6
    (20.23)
    47.0
    (57.13)
    39.3
    (27.78)
    5.2
    (3.61)
    28.6
    (41.11)
    Time from local/regional recurrence to consent for this study (median) (Weeks) [Median (Full Range) ]
    Median (Full Range) [Weeks]
    6.1
    18.6
    16.6
    15.4
    37.7
    5.6
    13.0
    Distant Metastases (Count of Participants)
    Yes
    3
    33.3%
    29
    76.3%
    11
    47.8%
    12
    100%
    5
    83.3%
    5
    83.3%
    65
    69.1%
    No
    6
    66.7%
    9
    23.7%
    12
    52.2%
    0
    0%
    1
    16.7%
    1
    16.7%
    29
    30.9%
    Histology (Count of Participants)
    Serous Epithelial Carcinoma
    9
    100%
    33
    86.8%
    21
    91.3%
    12
    100%
    4
    66.7%
    6
    100%
    85
    90.4%
    Endometrioid Carcinoma
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Clear Cell Epithelial Carcinoma
    0
    0%
    2
    5.3%
    1
    4.3%
    0
    0%
    1
    16.7%
    0
    0%
    4
    4.3%
    Transitional Cell/Brenner Carcinoma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Squamous Cell Epithelial Carcinoma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Undifferentiated Epithelial Carcinoma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Mucinous Epithelial Carcinoma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    1.1%
    Mixed Epithelial Carcinoma
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Missing
    0
    0%
    1
    2.6%
    1
    4.3%
    0
    0%
    0
    0%
    0
    0%
    2
    2.1%
    Histological Grade (Count of Participants)
    G1 - Well Differentiated
    1
    11.1%
    1
    2.6%
    0
    0%
    2
    16.7%
    0
    0%
    0
    0%
    4
    4.3%
    G2 - Moderately Differentiated
    0
    0%
    1
    2.6%
    1
    4.3%
    0
    0%
    0
    0%
    0
    0%
    2
    2.1%
    G3 - Poorly Differentiated
    5
    55.6%
    28
    73.7%
    15
    65.2%
    9
    75%
    5
    83.3%
    3
    50%
    65
    69.1%
    G4 - Undifferentiated
    0
    0%
    3
    7.9%
    2
    8.7%
    0
    0%
    1
    16.7%
    1
    16.7%
    7
    7.4%
    GX - Grade cannot be assessed or Not Applicable
    2
    22.2%
    3
    7.9%
    3
    13%
    1
    8.3%
    0
    0%
    2
    33.3%
    11
    11.7%
    Missing
    1
    11.1%
    2
    5.3%
    2
    8.7%
    0
    0%
    0
    0%
    0
    0%
    5
    5.3%
    Stage at Initial Diagnosis (Count of Participants)
    IC
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    IIC
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    1.1%
    III
    0
    0%
    1
    2.6%
    1
    4.3%
    0
    0%
    0
    0%
    0
    0%
    2
    2.1%
    IIIA
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    2
    2.1%
    IIIB
    0
    0%
    2
    5.3%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    3
    3.2%
    IIIC
    6
    66.7%
    14
    36.8%
    14
    60.9%
    4
    33.3%
    1
    16.7%
    5
    83.3%
    44
    46.8%
    IV
    3
    33.3%
    18
    47.4%
    8
    34.8%
    8
    66.7%
    2
    33.3%
    1
    16.7%
    40
    42.6%
    Missing
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Metastatic Disease (Count of Participants)
    Yes
    7
    77.8%
    37
    97.4%
    19
    82.6%
    12
    100%
    5
    83.3%
    6
    100%
    86
    91.5%
    No
    2
    22.2%
    1
    2.6%
    4
    17.4%
    0
    0%
    1
    16.7%
    0
    0%
    8
    8.5%
    Sites of Metastatic Disease (Number) [Number]
    Bone
    2
    22.2%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    3.2%
    Breast
    0
    0%
    0
    0%
    0
    0%
    2
    16.7%
    0
    0%
    0
    0%
    2
    2.1%
    Distant Lymph Nodes
    1
    11.1%
    14
    36.8%
    10
    43.5%
    8
    66.7%
    3
    50%
    1
    16.7%
    37
    39.4%
    Liver
    6
    66.7%
    13
    34.2%
    4
    17.4%
    3
    25%
    2
    33.3%
    3
    50%
    31
    33%
    Local or Regional Lymph Nodes
    4
    44.4%
    20
    52.6%
    12
    52.2%
    7
    58.3%
    1
    16.7%
    1
    16.7%
    45
    47.9%
    Lung
    1
    11.1%
    10
    26.3%
    3
    13%
    2
    16.7%
    1
    16.7%
    2
    33.3%
    19
    20.2%
    Other
    4
    44.4%
    31
    81.6%
    8
    34.8%
    9
    75%
    5
    83.3%
    2
    33.3%
    59
    62.8%
    Skin or Subcutaneous
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Prior Systemic Therapy (Count of Participants)
    Yes
    9
    100%
    38
    100%
    23
    100%
    12
    100%
    6
    100%
    6
    100%
    94
    100%
    No
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Time from end of most recent prior systemic therapy to consent for this trial (mean) (Weeks) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Weeks]
    11.0
    (9.54)
    14.4
    (15.45)
    10.5
    (7.81)
    15.4
    (15.12)
    12.9
    (11.36)
    13.4
    (12.08)
    13.1
    (12.75)
    Time from end of most recent prior systemic therapy to consent for this trial (median) (Weeks) [Median (Full Range) ]
    Median (Full Range) [Weeks]
    5.4
    6.9
    6.9
    9.4
    10.5
    12.2
    7.6
    Number of prior treatment regimens (Count of Participants)
    0
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3
    33.3%
    12
    31.6%
    8
    34.8%
    4
    33.3%
    3
    50%
    2
    33.3%
    32
    34%
    2
    6
    66.7%
    16
    42.1%
    9
    39.1%
    5
    41.7%
    3
    50%
    4
    66.7%
    43
    45.7%
    3
    0
    0%
    10
    26.3%
    6
    26.1%
    2
    16.7%
    0
    0%
    0
    0%
    18
    19.1%
    >3
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    1
    1.1%
    Disease setting for most recent prior regimen (Count of Participants)
    Neoadjuvant
    0
    0%
    4
    10.5%
    2
    8.7%
    2
    16.7%
    0
    0%
    1
    16.7%
    9
    9.6%
    Adjuvant
    4
    44.4%
    15
    39.5%
    13
    56.5%
    4
    33.3%
    4
    66.7%
    1
    16.7%
    41
    43.6%
    Metastatic
    5
    55.6%
    19
    50%
    8
    34.8%
    6
    50%
    2
    33.3%
    4
    66.7%
    44
    46.8%
    Disease setting for most recent prior regimen (Count of Participants)
    Adj/Neoadj in Localized disease (Stage I or II)
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    2
    2.1%
    Adjuvant in advanced disease (Stage III or IV)
    4
    44.4%
    14
    36.8%
    13
    56.5%
    4
    33.3%
    3
    50%
    1
    16.7%
    39
    41.5%
    Neoadjuvant in advanced disease (Stage III or IV)
    0
    0%
    3
    7.9%
    2
    8.7%
    2
    16.7%
    0
    0%
    1
    16.7%
    8
    8.5%
    Metastatic
    5
    55.6%
    19
    50%
    8
    34.8%
    6
    50%
    2
    33.3%
    4
    66.7%
    44
    46.8%
    Missing
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Best overall response to most recent prior regimen (Count of Participants)
    Complete Response (CR)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    2
    33.3%
    3
    3.2%
    Partial Response (PR)
    0
    0%
    2
    5.3%
    1
    4.3%
    1
    8.3%
    0
    0%
    1
    16.7%
    5
    5.3%
    Non-CR/Non-PD
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Stable Disease (SD)
    2
    22.2%
    4
    10.5%
    1
    4.3%
    2
    16.7%
    1
    16.7%
    0
    0%
    10
    10.6%
    Progressive Disease (PD)
    2
    22.2%
    9
    23.7%
    5
    21.7%
    4
    33.3%
    1
    16.7%
    2
    33.3%
    23
    24.5%
    Not Evaluable
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Not Applicable
    5
    55.6%
    21
    55.3%
    16
    69.6%
    5
    41.7%
    3
    50%
    1
    16.7%
    51
    54.3%
    Reason most recent prior regimen ended (Count of Participants)
    Completed planned treatment
    4
    44.4%
    14
    36.8%
    10
    43.5%
    5
    41.7%
    3
    50%
    2
    33.3%
    38
    40.4%
    Progressive Disease
    5
    55.6%
    19
    50%
    10
    43.5%
    7
    58.3%
    2
    33.3%
    3
    50%
    46
    48.9%
    Toxicity
    0
    0%
    3
    7.9%
    1
    4.3%
    0
    0%
    1
    16.7%
    1
    16.7%
    6
    6.4%
    Other
    0
    0%
    2
    5.3%
    2
    8.7%
    0
    0%
    0
    0%
    0
    0%
    4
    4.3%
    Prior Surgery (Count of Participants)
    Yes
    8
    88.9%
    35
    92.1%
    22
    95.7%
    11
    91.7%
    6
    100%
    6
    100%
    88
    93.6%
    No
    1
    11.1%
    3
    7.9%
    1
    4.3%
    1
    8.3%
    0
    0%
    0
    0%
    6
    6.4%
    Prior Radiotherapy (Count of Participants)
    Yes
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    No
    9
    100%
    37
    97.4%
    23
    100%
    12
    100%
    6
    100%
    6
    100%
    93
    98.9%
    Weight (mean) (Kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kilograms]
    73.5
    (21.56)
    73.2
    (15.89)
    75.7
    (19.25)
    70.6
    (9.45)
    70.2
    (14.11)
    65.7
    (8.61)
    72.8
    (16.12)
    Weight (median) (Kilograms) [Median (Full Range) ]
    Median (Full Range) [Kilograms]
    69.6
    69.6
    71.5
    67.7
    68.2
    67.8
    69.7
    Systolic Blood Pressure (mean) (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    130.0
    (15.23)
    125.2
    (13.37)
    127.7
    (10.65)
    122.3
    (6.40)
    125.2
    (17.22)
    127.5
    (9.35)
    126.1
    (12.16)
    Systolic Blood Pressure (median) (mmHg) [Median (Full Range) ]
    Median (Full Range) [mmHg]
    130.0
    126.5
    128.0
    121.0
    120.0
    126.5
    126.0
    Diastolic Blood Pressure (mean) (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    76.2
    (10.96)
    76.7
    (7.74)
    74.8
    (8.03)
    74.4
    (8.26)
    73.0
    (6.66)
    78.7
    (6.02)
    75.8
    (7.99)
    Diastolic Blood Pressure (median) (mmHg) [Median (Full Range) ]
    Median (Full Range) [mmHg]
    78.0
    78.0
    75.0
    73.5
    74.0
    77.5
    76.0
    Body Surface Area (mean) (m²) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m²]
    1.8
    (0.25)
    1.8
    (0.19)
    1.8
    (0.22)
    1.8
    (0.13)
    1.8
    (0.18)
    1.7
    (0.10)
    1.8
    (0.19)
    Body Surface Area (median) (m²) [Median (Full Range) ]
    Median (Full Range) [m²]
    1.8
    1.8
    1.8
    1.7
    1.7
    1.7
    1.7

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR)
    Description Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    1
    11.1%
    11
    28.9%
    7
    30.4%
    8
    66.7%
    2
    33.3%
    1
    16.7%
    2. Secondary Outcome
    Title Disease Control Rate (DCR)
    Description The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    3
    33.3%
    27
    71.1%
    19
    82.6%
    12
    100%
    3
    50%
    5
    83.3%
    3. Secondary Outcome
    Title Duration of Response (DoR)
    Description Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause.
    Time Frame Throughout the duration of the study, approximately 19 months.

    Outcome Measure Data

    Analysis Population Description
    Duration of Response (DoR) was calculated for all responders (N = 30)
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 1 11 7 8 2 1
    Median (95% Confidence Interval) [Months]
    4.4
    12.0
    NA
    10.4
    NA
    NA
    4. Secondary Outcome
    Title Progression Free Survival (Median, 80% CI)
    Description Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates.
    Time Frame Throughout the Study, Approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Median (80% Confidence Interval) [Months]
    1.7
    5.5
    4.2
    12.0
    2.7
    NA
    5. Secondary Outcome
    Title Progression Free Survival (Median, 95% CI)
    Description Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates.
    Time Frame Throughout the Study, Approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Median (95% Confidence Interval) [Months]
    1.7
    5.5
    4.2
    12.0
    2.7
    NA
    6. Secondary Outcome
    Title Overall Survival (Median, 80% CI)
    Description Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
    Time Frame Throughout the Study, Approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Median (80% Confidence Interval) [Months]
    16.0
    NA
    8.9
    19.2
    3.8
    NA
    7. Secondary Outcome
    Title Overall Survival (Median, 95% CI)
    Description Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
    Time Frame Throughout the Study, Approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Median (95% Confidence Interval) [Months]
    16.0
    NA
    8.9
    19.2
    6.2
    NA
    8. Secondary Outcome
    Title Gynecologic Cancer Intergroup (GCIG) CA-125 Response
    Description The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days.
    Time Frame Throughout the study, approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    The CA-125 analysis set was comprised of all dosed patients with pre-treatment serum sample showing CA-125 ≥ 2 x ULN within 2 weeks before starting treatment.
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 8 28 15 11 4 4
    Number (90% Confidence Interval) [Percent]
    25.0
    53.6
    26.7
    63.6
    25.0
    25.0
    9. Secondary Outcome
    Title The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
    Description The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number of patients with ≥1 TEAE of max Grade 1
    0
    0%
    2
    5.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Number of patients with ≥1 TEAE of max Grade 2
    1
    11.1%
    1
    2.6%
    5
    21.7%
    0
    0%
    3
    50%
    4
    66.7%
    Number of patients with ≥1 TEAE of max Grade 3
    2
    22.2%
    19
    50%
    10
    43.5%
    4
    33.3%
    3
    50%
    0
    0%
    Number of patients with ≥1 TEAE of max Grade 4
    6
    66.7%
    15
    39.5%
    8
    34.8%
    8
    66.7%
    0
    0%
    2
    33.3%
    Number of patients with ≥1 TEAE of max Grade 5
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
    Description The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number of patients with ≥1 TEAE of max Grade 1
    0
    0%
    3
    7.9%
    2
    8.7%
    0
    0%
    0
    0%
    0
    0%
    Number of patients with ≥1 TEAE of max Grade 2
    1
    11.1%
    4
    10.5%
    5
    21.7%
    0
    0%
    5
    83.3%
    4
    66.7%
    Number of patients with ≥1 TEAE of max Grade 3
    3
    33.3%
    16
    42.1%
    7
    30.4%
    4
    33.3%
    1
    16.7%
    0
    0%
    Number of patients with ≥1 TEAE of max Grade 4
    5
    55.6%
    14
    36.8%
    8
    34.8%
    8
    66.7%
    0
    0%
    2
    33.3%
    Number of patients with ≥1 TEAE of max Grade 5
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    11. Secondary Outcome
    Title The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
    Description The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number of patients with ≥1 TEAE of max Grade 1
    0
    0%
    4
    10.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Number of patients with ≥1 TEAE of max Grade 2
    1
    11.1%
    5
    13.2%
    6
    26.1%
    0
    0%
    5
    83.3%
    4
    66.7%
    Number of patients with ≥1 TEAE of max Grade 3
    3
    33.3%
    13
    34.2%
    8
    34.8%
    4
    33.3%
    1
    16.7%
    0
    0%
    Number of patients with ≥1 TEAE of max Grade 4
    5
    55.6%
    15
    39.5%
    8
    34.8%
    8
    66.7%
    0
    0%
    2
    33.3%
    Number of patients with ≥1 TEAE of max Grade 5
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12. Secondary Outcome
    Title Serious Adverse Events
    Description The number of patients experiencing at least one serious adverse event (SAE).
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Pts. with ≥ one serious TEAE related to AZD1775.
    0
    0%
    8
    21.1%
    9
    39.1%
    7
    58.3%
    1
    16.7%
    1
    16.7%
    Pts. with ≥ one serious TEAE related to Chemo.
    0
    0%
    8
    21.1%
    9
    39.1%
    7
    58.3%
    1
    16.7%
    1
    16.7%
    13. Secondary Outcome
    Title Serious Adverse Events Leading to Death
    Description The number of patients experiencing at least one serious adverse event (SAE) leading to death.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    No. with STEAE related to AZD1775 leading to death
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    No. with STEAE related to chemo leading to death
    0
    0%
    1
    2.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    14. Secondary Outcome
    Title Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
    Description The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    0
    0%
    6
    15.8%
    5
    21.7%
    1
    8.3%
    0
    0%
    0
    0%
    15. Secondary Outcome
    Title Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
    Description The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    2
    22.2%
    18
    47.4%
    5
    21.7%
    11
    91.7%
    0
    0%
    0
    0%
    16. Secondary Outcome
    Title Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
    Description The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    8
    88.9%
    30
    78.9%
    10
    43.5%
    11
    91.7%
    0
    0%
    1
    16.7%
    17. Secondary Outcome
    Title Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
    Description The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    0
    0%
    6
    15.8%
    5
    21.7%
    1
    8.3%
    0
    0%
    0
    0%
    18. Secondary Outcome
    Title Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
    Description The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    6
    66.7%
    19
    50%
    8
    34.8%
    11
    91.7%
    0
    0%
    0
    0%
    19. Secondary Outcome
    Title Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
    Description The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
    Time Frame Throughout the duration of the study (up to 19 months)

    Outcome Measure Data

    Analysis Population Description
    This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 9 38 23 12 6 6
    Number [Participants]
    8
    88.9%
    28
    73.7%
    12
    52.2%
    9
    75%
    0
    0%
    1
    16.7%
    20. Secondary Outcome
    Title Single Dose Adavosertib Cmax
    Description Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
    Time Frame Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

    Outcome Measure Data

    Analysis Population Description
    The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
    Arm/Group Title Arm A 800 mg/m² Gemcitabine Arm A 1000 mg/m² Gemcitabine Arm B Arm C
    Arm/Group Description Adavosertib175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 1000 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles.
    Measure Participants 3 4 7 6
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    477.4
    (3.776)
    571.1
    (29.79)
    533.8
    (37.29)
    556.6
    (56.39)
    21. Secondary Outcome
    Title Multiple Dose Adavosertib Cmax
    Description Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
    Time Frame Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

    Outcome Measure Data

    Analysis Population Description
    The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
    Arm/Group Title Arm D 175 mg Arm D 225 mg
    Arm/Group Description Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 5 4
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    4135
    (65.8)
    23530
    (30.15)
    22. Secondary Outcome
    Title Single Dose Adavosertib Tmax
    Description The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
    Time Frame Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

    Outcome Measure Data

    Analysis Population Description
    The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
    Arm/Group Title Arm A 800 mg/m² Gemcitabine Arm A 1000 mg/m² Gemcitabine Arm B Arm C
    Arm/Group Description Adavosertib175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 1000 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles.
    Measure Participants 3 4 7 6
    Median (Full Range) [hours]
    2.00
    2.02
    4.08
    3.15
    23. Secondary Outcome
    Title Multiple Dose Adavosertib Tmax
    Description The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
    Time Frame Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

    Outcome Measure Data

    Analysis Population Description
    The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
    Arm/Group Title Arm D 175 mg Arm D 225 mg
    Arm/Group Description Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    Measure Participants 5 4
    Median (Full Range) [hours]
    3.92
    2.88

    Adverse Events

    Time Frame Throughout the study, approximately 19 months
    Adverse Event Reporting Description
    Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles. Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles. Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.
    All Cause Mortality
    Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/9 (55.6%) 12/38 (31.6%) 9/23 (39.1%) 2/12 (16.7%) 3/6 (50%) 0/6 (0%)
    Serious Adverse Events
    Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/9 (44.4%) 17/38 (44.7%) 12/23 (52.2%) 8/12 (66.7%) 2/6 (33.3%) 1/6 (16.7%)
    Blood and lymphatic system disorders
    Anaemia 0/9 (0%) 0 0/38 (0%) 0 4/23 (17.4%) 4 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Febrile Neutropenia 0/9 (0%) 0 3/38 (7.9%) 5 2/23 (8.7%) 2 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Leukopenia 0/9 (0%) 0 0/38 (0%) 0 1/23 (4.3%) 1 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Neutropenia 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 2/12 (16.7%) 2 0/6 (0%) 0 1/6 (16.7%) 1
    Pancytopenia 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Thrombocytopenia 0/9 (0%) 0 0/38 (0%) 0 3/23 (13%) 3 5/12 (41.7%) 6 0/6 (0%) 0 0/6 (0%) 0
    Cardiac disorders
    Atrial Fibrillation 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal Pain 0/9 (0%) 0 0/38 (0%) 0 1/23 (4.3%) 1 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Colitis 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Diarrhoea 0/9 (0%) 0 0/38 (0%) 0 2/23 (8.7%) 2 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Ileus 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Intestinal Obstruction 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Nausea 1/9 (11.1%) 1 1/38 (2.6%) 1 2/23 (8.7%) 3 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Small Intestinal Obstruction 2/9 (22.2%) 3 3/38 (7.9%) 6 1/23 (4.3%) 2 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Vomiting 1/9 (11.1%) 1 1/38 (2.6%) 1 2/23 (8.7%) 3 1/12 (8.3%) 1 1/6 (16.7%) 1 0/6 (0%) 0
    General disorders
    Fatigue 1/9 (11.1%) 1 0/38 (0%) 0 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Pyrexia 1/9 (11.1%) 1 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Anaphylactic Reaction 0/9 (0%) 0 0/38 (0%) 0 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Immune system disorders
    Chest Pain 0/9 (0%) 0 0/38 (0%) 0 1/23 (4.3%) 1 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Bacteraemia 0/9 (0%) 0 3/38 (7.9%) 4 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Cellulitis 1/9 (11.1%) 1 1/38 (2.6%) 2 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Kidney Infection 0/9 (0%) 0 0/38 (0%) 0 0/23 (0%) 0 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Liver Abscess 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Neutropenic Sepsis 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Paraspinal Abscess 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Sepsis 1/9 (11.1%) 2 0/38 (0%) 0 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Septic Shock 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Urinary Tract Infection 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Vascular Device Infection 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Gastrointestinal Stoma Complication 0/9 (0%) 0 0/38 (0%) 0 1/23 (4.3%) 1 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Infusion Related Reaction 0/9 (0%) 0 0/38 (0%) 0 2/23 (8.7%) 2 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Investigations
    Neutrophil Count Decreased 0/9 (0%) 0 0/38 (0%) 0 1/23 (4.3%) 1 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Platelet Count Decreased 0/9 (0%) 0 0/38 (0%) 0 2/23 (8.7%) 2 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Metabolism and nutrition disorders
    Type 2 Diabetes Mellitus 0/9 (0%) 0 0/38 (0%) 0 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Musculoskeletal and connective tissue disorders
    Flank Pain 1/9 (11.1%) 1 0/38 (0%) 0 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Transient Ischaemic Attack 0/9 (0%) 0 1/38 (2.6%) 1 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/9 (0%) 0 0/38 (0%) 0 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Pulmonary Embolism 0/9 (0%) 0 1/38 (2.6%) 2 1/23 (4.3%) 1 2/12 (16.7%) 2 0/6 (0%) 0 0/6 (0%) 0
    Wheezing 0/9 (0%) 0 0/38 (0%) 0 0/23 (0%) 0 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Skin and subcutaneous tissue disorders
    Skin Ulcer 0/9 (0%) 0 0/38 (0%) 0 0/23 (0%) 0 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 38/38 (100%) 23/23 (100%) 12/12 (100%) 6/6 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 3/9 (33.3%) 12 24/38 (63.2%) 82 13/23 (56.5%) 45 9/12 (75%) 48 3/6 (50%) 4 2/6 (33.3%) 2
    Neutropenia 4/9 (44.4%) 14 12/38 (31.6%) 25 5/23 (21.7%) 14 11/12 (91.7%) 51 1/6 (16.7%) 1 2/6 (33.3%) 8
    Thrombocytopenia 1/9 (11.1%) 3 9/38 (23.7%) 12 11/23 (47.8%) 33 11/12 (91.7%) 90 0/6 (0%) 0 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal Distension 2/9 (22.2%) 3 2/38 (5.3%) 2 3/23 (13%) 3 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Abdominal Pain 2/9 (22.2%) 2 8/38 (21.1%) 12 8/23 (34.8%) 9 1/12 (8.3%) 4 1/6 (16.7%) 2 2/6 (33.3%) 3
    Constipation 1/9 (11.1%) 1 4/38 (10.5%) 4 5/23 (21.7%) 7 4/12 (33.3%) 4 2/6 (33.3%) 2 0/6 (0%) 0
    Diarrhoea 3/9 (33.3%) 3 31/38 (81.6%) 67 16/23 (69.6%) 33 6/12 (50%) 11 1/6 (16.7%) 1 5/6 (83.3%) 9
    Dyspepsia 1/9 (11.1%) 1 3/38 (7.9%) 3 2/23 (8.7%) 2 1/12 (8.3%) 1 0/6 (0%) 0 2/6 (33.3%) 2
    Gastrointestinal Reflux Disease 0/9 (0%) 0 4/38 (10.5%) 4 1/23 (4.3%) 2 0/12 (0%) 0 3/6 (50%) 3 0/6 (0%) 0
    Nausea 5/9 (55.6%) 9 23/38 (60.5%) 49 19/23 (82.6%) 38 10/12 (83.3%) 12 4/6 (66.7%) 5 4/6 (66.7%) 7
    Stomatitis 0/9 (0%) 0 3/38 (7.9%) 3 2/23 (8.7%) 2 1/12 (8.3%) 2 2/6 (33.3%) 4 1/6 (16.7%) 1
    Vomiting 4/9 (44.4%) 7 19/38 (50%) 41 13/23 (56.5%) 24 4/12 (33.3%) 9 3/6 (50%) 3 0/6 (0%) 0
    General disorders
    Fatigue 3/9 (33.3%) 5 23/38 (60.5%) 33 17/23 (73.9%) 30 8/12 (66.7%) 11 3/6 (50%) 6 5/6 (83.3%) 5
    Oedema, Peripheral 0/9 (0%) 0 10/38 (26.3%) 10 0/23 (0%) 0 5/12 (41.7%) 5 0/6 (0%) 0 0/6 (0%) 0
    Pyrexia 4/9 (44.4%) 4 8/38 (21.1%) 11 1/23 (4.3%) 1 0/12 (0%) 0 1/6 (16.7%) 3 0/6 (0%) 0
    Infections and infestations
    Urinary Tract Infection 0/9 (0%) 0 6/38 (15.8%) 9 2/23 (8.7%) 3 1/12 (8.3%) 1 1/6 (16.7%) 1 1/6 (16.7%) 2
    Investigations
    Alanine Aminotransferase Increased 3/9 (33.3%) 3 2/38 (5.3%) 2 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Aspartate Aminotransferase Increased 1/9 (11.1%) 3 4/38 (10.5%) 11 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Blood Alkaline Phosphatase Increased 0/9 (0%) 0 3/38 (7.9%) 5 2/23 (8.7%) 3 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Blood Creatinine Increased 0/9 (0%) 0 3/38 (7.9%) 3 1/23 (4.3%) 2 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Neutrophil Count Decreased 4/9 (44.4%) 16 13/38 (34.2%) 64 5/23 (21.7%) 17 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Platelet Count Decreased 2/9 (22.2%) 10 7/38 (18.4%) 12 5/23 (21.7%) 19 0/12 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Weight Decreased 1/9 (11.1%) 1 3/38 (7.9%) 3 2/23 (8.7%) 2 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    White Blood Cell Count Decreased 2/9 (22.2%) 10 11/38 (28.9%) 64 4/23 (17.4%) 17 0/12 (0%) 0 1/6 (16.7%) 1 1/6 (16.7%) 1
    Metabolism and nutrition disorders
    Decreased Appetite 2/9 (22.2%) 3 7/38 (18.4%) 9 5/23 (21.7%) 5 1/12 (8.3%) 1 1/6 (16.7%) 1 0/6 (0%) 0
    Dehydration 0/9 (0%) 0 3/38 (7.9%) 3 2/23 (8.7%) 4 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Hyperglycaemia 1/9 (11.1%) 2 6/38 (15.8%) 12 3/23 (13%) 3 0/12 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Hypoalbuminaemia 0/9 (0%) 0 6/38 (15.8%) 18 0/23 (0%) 0 2/12 (16.7%) 2 0/6 (0%) 0 0/6 (0%) 0
    Hypokalaemia 1/9 (11.1%) 1 4/38 (10.5%) 6 2/23 (8.7%) 8 3/12 (25%) 4 1/6 (16.7%) 1 0/6 (0%) 0
    Hypomagnesaemia 1/9 (11.1%) 1 8/38 (21.1%) 13 6/23 (26.1%) 8 2/12 (16.7%) 3 0/6 (0%) 0 0/6 (0%) 0
    Hyponatraemia 1/9 (11.1%) 7 4/38 (10.5%) 6 1/23 (4.3%) 1 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Hypophosphataemia 0/9 (0%) 0 3/38 (7.9%) 5 0/23 (0%) 0 2/12 (16.7%) 2 0/6 (0%) 0 0/6 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/9 (22.2%) 2 1/38 (2.6%) 1 2/23 (8.7%) 2 3/12 (25%) 3 0/6 (0%) 0 0/6 (0%) 0
    Back Pain 1/9 (11.1%) 1 6/38 (15.8%) 6 4/23 (17.4%) 5 3/12 (25%) 3 1/6 (16.7%) 1 0/6 (0%) 0
    Bone Pain 1/9 (11.1%) 1 1/38 (2.6%) 1 1/23 (4.3%) 2 2/12 (16.7%) 2 0/6 (0%) 0 0/6 (0%) 0
    Myalgia 0/9 (0%) 0 6/38 (15.8%) 6 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Pain in Extremity 1/9 (11.1%) 1 4/38 (10.5%) 4 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Dizziness 0/9 (0%) 0 2/38 (5.3%) 2 3/23 (13%) 5 1/12 (8.3%) 1 0/6 (0%) 0 2/6 (33.3%) 3
    Dysgeusia 1/9 (11.1%) 1 4/38 (10.5%) 4 3/23 (13%) 4 4/12 (33.3%) 4 1/6 (16.7%) 1 0/6 (0%) 0
    Headache 1/9 (11.1%) 1 8/38 (21.1%) 8 7/23 (30.4%) 9 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Peripheral Sensory Neuropathy 0/9 (0%) 0 8/38 (21.1%) 14 0/23 (0%) 0 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Psychiatric disorders
    Insomnia 1/9 (11.1%) 1 6/38 (15.8%) 6 2/23 (8.7%) 5 1/12 (8.3%) 1 1/6 (16.7%) 1 0/6 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/9 (0%) 0 5/38 (13.2%) 5 3/23 (13%) 3 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Dyspnoea 1/9 (11.1%) 1 10/38 (26.3%) 12 4/23 (17.4%) 4 4/12 (33.3%) 6 0/6 (0%) 0 1/6 (16.7%) 2
    Epistaxis 1/9 (11.1%) 1 2/38 (5.3%) 2 2/23 (8.7%) 4 1/12 (8.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Nasal Congestion 0/9 (0%) 0 5/38 (13.2%) 7 2/23 (8.7%) 2 0/12 (0%) 0 0/6 (0%) 0 0/6 (0%) 0
    Oropharyngeal Pain 1/9 (11.1%) 1 2/38 (5.3%) 3 1/23 (4.3%) 1 2/12 (16.7%) 2 0/6 (0%) 0 0/6 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 0/9 (0%) 0 6/38 (15.8%) 6 0/23 (0%) 0 1/12 (8.3%) 1 1/6 (16.7%) 1 0/6 (0%) 0
    Pruritus 2/9 (22.2%) 4 1/38 (2.6%) 1 3/23 (13%) 5 0/12 (0%) 0 1/6 (16.7%) 1 1/6 (16.7%) 1
    Rash 3/9 (33.3%) 3 2/38 (5.3%) 2 0/23 (0%) 0 1/12 (8.3%) 1 1/6 (16.7%) 2 0/6 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Pejvack Motlagh, MD
    Organization AstraZeneca
    Phone +44 (0) 7384 799 850
    Email pejvack.motlagh@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02272790
    Other Study ID Numbers:
    • D6010C00004
    • GYN 49
    First Posted:
    Oct 23, 2014
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Aug 1, 2022