Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Official Title
A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Acronym
Not provided
Organization
AstraZenecaINDUSTRY
Status Module
Record Verification Date
Aug 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 30, 2015Actual
Primary Completion Date
Dec 13, 2018Actual
Completion Date
Mar 8, 2023Actual
First Submitted Date
Oct 14, 2014
First Submission Date that Met QC Criteria
Oct 21, 2014
First Posted Date
Oct 23, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 4, 2019
Results First Submitted that Met QC Criteria
Nov 4, 2019
Results First Posted Date
Nov 22, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 2, 2023
Last Update Posted Date
Oct 3, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AstraZenecaINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.
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.
Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
95Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm A (adavosertib + gemcitabine)
Experimental
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
Drug: Gemcitabine
Arm B (adavosertib + paclitaxel)
Experimental
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
Drug: Paclitaxel
Arm C/C2 (adavosertib + carboplatin)
Experimental
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
Drug: Carboplatin
Arm D (adavosertib + PLD)
Experimental
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.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Adavosertib
Drug
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
Arm A (adavosertib + gemcitabine)
Arm B (adavosertib + paclitaxel)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
Throughout the duration of the study (up to 19 months)
Secondary Outcomes
Measure
Description
Time Frame
Disease Control Rate (DCR)
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.
Throughout the duration of the study (up to 19 months)
Duration of Response (DoR)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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:
ANC ≥1500/μL
HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
Platelets ≥ 100,000/μL
ALT & AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
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.
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:
Unstable angina pectoris
Congestive heart failure
Acute myocardial infarction
Conduction abnormality not controlled with pacemaker or medication
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.
Accepts Healthy Volunteers
No
Sex
Female
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
130 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Kathleen Moore, MD
Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Moore KN, Chambers SK, Hamilton EP, Chen LM, Oza AM, Ghamande SA, Konecny GE, Plaxe SC, Spitz DL, Geenen JJJ, Troso-Sandoval TA, Cragun JM, Rodrigo Imedio E, Kumar S, Mugundu GM, Lai Z, Chmielecki J, Jones SF, Spigel DR, Cadoo KA. Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study. Clin Cancer Res. 2022 Jan 1;28(1):36-44. doi: 10.1158/1078-0432.CCR-21-0158. Epub 2021 Oct 13.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at:
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:
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.
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Arm A
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.
FG001
Arm B
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.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Sep 5, 2018
Nov 4, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
United Kingdom
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Adavosertib
Drug: PLD
Arm C/C2 (adavosertib + carboplatin)
Arm D (adavosertib + PLD)
MK1775
Paclitaxel
Drug
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.
Arm B (adavosertib + paclitaxel)
Taxol
Carboplatin
Drug
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.
Arm C/C2 (adavosertib + carboplatin)
Paraplatin
Gemcitabine
Drug
Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.
Arm A (adavosertib + gemcitabine)
PLD
Drug
PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.
Arm D (adavosertib + PLD)
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.
Throughout the duration of the study, approximately 19 months.
Progression Free Survival (Median, 80% CI)
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.
Throughout the Study, Approximately 4 years
Progression Free Survival (Median, 95% CI)
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.
Throughout the Study, Approximately 4 years
Overall Survival (Median, 80% CI)
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.
Throughout the Study, Approximately 4 years
Overall Survival (Median, 95% CI)
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.
Throughout the Study, Approximately 4 years
Gynecologic Cancer Intergroup (GCIG) CA-125 Response
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.
Throughout the study, approximately 4 years
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade.
Throughout the duration of the study (up to 19 months)
Serious Adverse Events
The number of patients experiencing at least one serious adverse event (SAE).
Throughout the duration of the study (up to 19 months)
Serious Adverse Events Leading to Death
The number of patients experiencing at least one serious adverse event (SAE) leading to death.
Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
Throughout the duration of the study (up to 19 months)
Single Dose Adavosertib Cmax
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.
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.
Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Single Dose Adavosertib Tmax
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.
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.
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.
FG003
Arm C2
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.
FG004
Arm D-175 mg
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.
FG005
Arm D-225 mg
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.
FG0009 subjects
FG00139 subjects
FG00223 subjects
FG00312 subjects
FG0046 subjects
FG0056 subjects
COMPLETED
FG0009 subjects
FG00138 subjects
FG00223 subjects
FG00312 subjects
FG0046 subjects
FG0056 subjects
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Physician Decision
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Arm A
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.
BG001
Arm B
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.
BG002
Arm C
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.
BG003
Arm C2
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.
BG004
Arm D-175 mg
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.
BG005
Arm D-225 mg
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.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0009
BG00138
BG00223
BG00312
BG0046
BG0056
BG00694
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG00223
ParticipantsBG003
Age, Continuous
Median
Full Range
years
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Region of Enrollment
Number
Participants
Title
Denominators
Categories
United States
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
< 65
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
ECOG Performance Status
ECOG Performance Status: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out light or sedentary work; 2 = Ambulatory and capable of all self care but unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, cannot carry on any self care. Totally confined to bed or chair; 5 = Dead.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG001
Time from 1st positive biopsy for disease to consent for this study (mean)
Mean
Standard Deviation
Weeks
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Time from 1st positive biopsy for disease to consent for this study (median)
Median
Full Range
Days
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Local or Regional Recurrence
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Time from local/regional recurrence to consent for this study (mean)
Sixty-seven (67) patients has a local or regional recurrence.
Sixty-seven (67) patients has a local or regional recurrence.
Mean
Standard Deviation
Weeks
Title
Denominators
Categories
ParticipantsBG0005
ParticipantsBG00126
ParticipantsBG002
Time from local/regional recurrence to consent for this study (median)
Sixty-seven (67) patients has a local or regional recurrence.
Sixty-seven (67) patients has a local or regional recurrence.
Median
Full Range
Weeks
Title
Denominators
Categories
ParticipantsBG0005
ParticipantsBG00126
ParticipantsBG002
Distant Metastases
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Histology
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Histological Grade
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Stage at Initial Diagnosis
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Metastatic Disease
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Sites of Metastatic Disease
Number
Participants
Title
Denominators
Categories
Bone
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Prior Systemic Therapy
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Time from end of most recent prior systemic therapy to consent for this trial (mean)
Mean
Standard Deviation
Weeks
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Time from end of most recent prior systemic therapy to consent for this trial (median)
Median
Full Range
Weeks
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Number of prior treatment regimens
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Disease setting for most recent prior regimen
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Disease setting for most recent prior regimen
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Best overall response to most recent prior regimen
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Reason most recent prior regimen ended
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Prior Surgery
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Prior Radiotherapy
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Weight (mean)
Mean
Standard Deviation
Kilograms
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Weight (median)
Median
Full Range
Kilograms
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Systolic Blood Pressure (mean)
Mean
Standard Deviation
mmHg
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Systolic Blood Pressure (median)
Median
Full Range
mmHg
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Diastolic Blood Pressure (mean)
Mean
Standard Deviation
mmHg
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Diastolic Blood Pressure (median)
Median
Full Range
mmHg
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Body Surface Area (mean)
Mean
Standard Deviation
m²
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Body Surface Area (median)
Median
Full Range
m²
Title
Denominators
Categories
ParticipantsBG0009
ParticipantsBG00138
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
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.
OG004
Arm D-175 mg
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.
OG005
Arm D-225 mg
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.
Units
Counts
Participants
OG0009
OG00138
OG00223
OG003
Title
Denominators
Categories
Title
Measurements
OG0001
OG00111
OG0027
OG003
Secondary
Disease Control Rate (DCR)
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.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Duration of Response (DoR)
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.
Duration of Response (DoR) was calculated for all responders (N = 30)
Posted
Median
95% Confidence Interval
Months
Throughout the duration of the study, approximately 19 months.
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
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.
Secondary
Progression Free Survival (Median, 80% CI)
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.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Median
80% Confidence Interval
Months
Throughout the Study, Approximately 4 years
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
Secondary
Progression Free Survival (Median, 95% CI)
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.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Median
95% Confidence Interval
Months
Throughout the Study, Approximately 4 years
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
Secondary
Overall Survival (Median, 80% CI)
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.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Median
80% Confidence Interval
Months
Throughout the Study, Approximately 4 years
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Overall Survival (Median, 95% CI)
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.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Median
95% Confidence Interval
Months
Throughout the Study, Approximately 4 years
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Gynecologic Cancer Intergroup (GCIG) CA-125 Response
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.
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.
Posted
Number
90% Confidence Interval
Percent
Throughout the study, approximately 4 years
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Secondary
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
Secondary
Serious Adverse Events
The number of patients experiencing at least one serious adverse event (SAE).
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
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.
Secondary
Serious Adverse Events Leading to Death
The number of patients experiencing at least one serious adverse event (SAE) leading to death.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
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.
Secondary
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Posted
Number
Participants
Throughout the duration of the study (up to 19 months)
ID
Title
Description
OG000
Arm A
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.
OG001
Arm B
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.
OG002
Arm C
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.
OG003
Arm C2
Secondary
Single Dose Adavosertib Cmax
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.
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.
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.
OG001
Arm A 1000 mg/m² Gemcitabine
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.
OG002
Arm B
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.
Secondary
Multiple Dose Adavosertib Cmax
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nM
Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
ID
Title
Description
OG000
Arm D 175 mg
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.
OG001
Arm D 225 mg
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.
Units
Counts
Participants
Secondary
Single Dose Adavosertib Tmax
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.
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.
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.
OG001
Arm A 1000 mg/m² Gemcitabine
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.
OG002
Arm B
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.
Secondary
Multiple Dose Adavosertib Tmax
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.
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.
Posted
Median
Full Range
hours
Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
ID
Title
Description
OG000
Arm D 175 mg
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.
OG001
Arm D 225 mg
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.
Units
Counts
Participants
Time Frame
Throughout the study, approximately 19 months
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Arm A
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.
5
9
4
9
9
9
EG001
Arm B
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.
12
38
17
38
38
38
EG002
Arm C
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.
9
23
12
23
23
23
EG003
Arm C2
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.
2
12
8
12
12
12
EG004
Arm D-175 mg
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.
3
6
2
6
6
6
EG005
Arm D-225 mg
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.