Ovarian Brenner Tumor, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Malignant Mixed Mesodermal (Mullerian) Tumor, Ovarian Mucinous Cystadenocarcinoma, Ovarian Seromucinous Carcinoma, Ovarian Serous Cystadenocarcinoma, Ovarian Serous Surface Papillary Adenocarcinoma, Ovarian Undifferentiated Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
Conditions
Brief summary
This randomized phase II clinical trial studies how well gemcitabine hydrochloride and WEE1 inhibitor MK-1775 work compared to gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of time. Gemcitabine hydrochloride may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA, molecules that contain instructions for the proper development and functioning of cells), which in turn stops the tumor from growing. The protein WEE1 may help to repair the damaged tumor cells, so the tumor continues to grow. WEE1 inhibitor MK-1775 may block the WEE1 protein activity and may increase the effectiveness of gemcitabine hydrochloride by preventing the WEE1 protein from repairing damaged tumor cells without causing harm to normal cells. It is not yet known whether gemcitabine hydrochloride with or without WEE1 inhibitor MK-1775 may be an effective treatment for recurrent ovarian, primary peritoneal, or fallopian tube cancer.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine (gemcitabine hydrochloride) in combination with AZD 1775 (MK-1775 \[WEE1 inhibitor MK-1775\]) compared to subjects receiving gemcitabine in combination with placebo. SECONDARY OBJECTIVES: I. To evaluate the objective response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of patients receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo. II. To evaluate the Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)125 response rate of patients receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo. III. To evaluate the overall survival of patients (max 1-year \[yr\] follow-up) receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo. IV. To evaluate the safety and tolerability of the combination of gemcitabine combined with AZD 1775 (MK-1775) in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. V. To evaluate tumor protein p53 (TP53) mutations (presence of mutation and type of mutation) as potential predictive factors of benefit (defined as response or progression-free survival \[PFS\] prolongation) to AZD 1775 (MK-1775) and gemcitabine treatment. VI. To evaluate p53 protein expression by immunohistochemistry as potential predictive factors of benefit (defined as response or PFS prolongation) to AZD 1775 (MK-1775) and gemcitabine treatment. TERTIARY OBJECTIVES: I. To evaluate patient reported outcomes using Patient-Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE). II. To evaluate the concordance of TP53 mutations in the tumor specimen and TP53 mutations determined by tagged-amplicon deep sequencing (Tam-Seq) in circulating tumor DNA. III. To correlate the levels circulating DNA TP53 mutations by Tam-Seq with response. IV. Validation of phosphorylated-cyclin-dependent cycle 2 (pCDC2) and gamma-H2A histone family, member X (H2AX) in skin and tumor tissue as a pharmacodynamic marker of therapy. V. To correlate changes in pCDC2 and gamma-H2AX with survival outcomes and response rate. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive WEE1 inhibitor MK-1775 orally (PO) on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride as patients in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-8 weeks (after the 30-37 day safety visit) for up to 1 year.
Interventions
DRUGAdavosertib
Given PO
DRUGGemcitabine Hydrochloride
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
OTHERPlacebo Administration
Given PO
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically confirmed epithelial ovarian, primary peritoneal and fallopian tube carcinoma; all histologic subtypes of epithelial ovarian cancer are eligible, but only patients with high grade serous ovarian cancer will be considered for the statistical analysis; non-high grade serous cancers will be allowed in an exploratory cohort * Patients must be platinum-resistant (platinum-free interval \< 6 months) or have platinum-refractory disease as per Gynecologic Cancer Intergroup Committee (GCIC) criteria; disease progression has to be radiologic or clinical; biomarker progression with CA125 after a platinum based regimen would not be sufficient evidence of disease progression; the patients must have had radiological progression to that regimen * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \> 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam * There is no limitation in the number of prior lines of therapy * Patients must have completed any prior chemotherapy, radiotherapy or major surgery at least 4 weeks before receiving study treatment; ongoing toxicities related to treatment must be =\< grade 1 and patients with grade 2 alopecia or peripheral neuropathy can also be included; palliative radiation to \< 10% of bone marrow is permissible if completed within one week of commencing study treatment as long as the toxicities secondary to palliative radiotherapy are limited to grade 1; the lesions that have received radiation treatment immediately before will be excluded as target lesions; previously irradiated lesions can be considered as targeted lesions, as long as there is prove of radiological progression * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Life expectancy of greater than 3 months * Leukocytes \>= 3,000/mcL * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Hemoglobin \>= 90 g/L * Blood transfusions are allowed at any time during the screening, treatment or follow-up period, according to the center recommendations * Prothrombin time (PT), partial thromboplastin time (PTT) and international normalized ratio (INR) =\< 1.5 upper limit of normal (ULN) * Total bilirubin =\< 1.5 x institutional upper limit of normal; unless due to Gilbert's syndrome * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal (5 x if liver metastases) * Creatinine =\< 1.5 × institutional upper limit of normal OR creatinine clearance \>= 40 mL/min/1.73 m\^2 for patients with creatinine levels above 1.5 x institutional limit of normal * Patients must be able to tolerate oral medication and not have evidence of active bowel obstruction * Note: patients can have a history of prior bowel obstruction, provided the patient is not having symptoms of bowel obstruction at the time of enrolment and the bowel obstruction is not anticipated to recur during the participation in the study * Patients must have disease amenable to biopsy and must be willing to undergo a paired biopsy for correlative analyses (the first biopsy within 28 days prior to start of treatment and the second biopsy while on treatment) * Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately * Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopause is defined as amenorrhea \>= 12 consecutive months; Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible reason * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patients who previously received gemcitabine for the treatment of recurrent disease * Patients who are receiving any other investigational agents * Patients with clinically or radiologically unstable brain metastases are excluded from this clinical trial * Note: patients with stable brain metastases after treatment, for at least 3 months prior to enrolling on this trial, could participate in the study; patients should be off, or on a stable dose of steroids * History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD 1775 (MK-1775) or gemcitabine * Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication * Pregnant and breastfeeding women are excluded from this study * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible * Uncontrolled intercurrent illness including, but not limited to, myocardial infarction within 6 months, congestive heart failure, symptomatic congestive heart failure, unstable angina pectoris, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, active liver disease or cerebrovascular disease with previous stroke, or psychiatric illness/social situations that would limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | From start of treatment until date of progression or death, whichever occurs first, up to 1 year follow-up | To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine in combination with AZD1775 compared to subjects receiving gemcitabine in combination with placebo. Progression is defined, using the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guideline, as at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | From start of treatment, every 6-8 weeks, until time of progression or death, whichever occurs first, up to 1 year follow-up | To evaluate the objective response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) of patients receiving gemcitabine combined with AZD1775 compared to patients receiving gemcitabine in combination with placebo. RECIST v1.1 criteria used for evaluation of target lesions: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), at least a 20% increase in the sum of the diameters of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The Best Overall Response is the best response recorded from the start of the treatment until disease progression/recurrence . |
| Response According to CA125 Criteria | From start of treatment, every 4 weeks, until time of progression or death, whichever occurs first, up to 1 year follow-up | To evaluate the GCIG CA125 response rate of patients receiving gemcitabine combined with AZD1775 compared to patients receiving gemcitabine in combination with placebo. A response according to CA-125 has occurred if there is at least a 50% reduction in CA-125 levels from a pre-treatment sample. The response must be confirmed and maintained for at least 28 days. |
| Overall Survival | From start of study treatment, every 12 weeks, until death, up to 22 months follow-up | To evaluate the overall survival of patients receiving gemcitabine combined with AZD1775 compared to patients receiving gemcitabine in combination with placebo. |
| Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | From start of treatment until AE resolution, stabilization, or improvement to less than grade 2, up to 1 year follow-up | To evaluate the safety and tolerability of the combination of gemcitabine combined with AZD1775 in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. |
| TP53 Mutations | Baseline | To evaluate TP53 mutations (presence of mutation and type of mutation) as potential predictive factors of benefit (defined as response or PFS prolongation) to AZD1775 and gemcitabine treatment. TP53 status was assessed using Sanger sequencing. |
| p53 Protein Expression | Baseline | To evaluate p53 protein expression by immunohistochemistry as potential predictive factors of benefit (defined as response or PFS prolongation) to AZD1775 and gemcitabine treatment. Evaluating p53 expression in patients with high-grade serous ovarian cancer and in patients with high-grade serous ovarian cancer with TP53 mutations. |
Countries
Canada, Singapore, United States
Contacts
PRINCIPAL_INVESTIGATORAmit M Oza
University Health Network-Princess Margaret Hospital
Participant flow
Recruitment details
Between Oct. 16, 2014 and Jan. 16, 2018, 124 women were enrolled, of whom 99 had high-grade serous ovarian cancer and were randomly assigned to AZD1775 plus gemcitabine (65 \[66%\]) or placebo plus gemcitabine (34 \[34%\]). 25 women with non-high-grade serous ovarian cancer were enrolled in the exploratory cohort.
Pre-assignment details
After randomization, five patients with high-grade serous ovarian cancer were found to be ineligible (four in the experimental group and one in the control group) and did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) Patients receive WEE1 inhibitor AZD1775 PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 61 |
| Arm II (Placebo, Gemcitabine Hydrochloride) Patients receive placebo PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride as patients in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 33 |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine Patients with non-high-grade serous histology were enrolled in an exploratory single-arm cohort and received WEE1 inhibitor AZD1775 PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 25 |
| Total | 119 |
Baseline characteristics
| Characteristic | Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Arm II (Placebo, Gemcitabine Hydrochloride) | Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 12 Participants | 5 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 21 Participants | 20 Participants | 83 Participants |
| Age, Continuous | 62 years | 63 years | 58 years | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 2 Participants | 7 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 48 Participants | 27 Participants | 16 Participants | 91 Participants |
| Region of Enrollment Canada | 38 Participants | 25 Participants | 12 Participants | 75 Participants |
| Region of Enrollment United States | 23 Participants | 8 Participants | 13 Participants | 44 Participants |
| Sex: Female, Male Female | 61 Participants | 33 Participants | 25 Participants | 119 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 50 / 61 | 30 / 33 | 16 / 25 |
| other Total, other adverse events | 61 / 61 | 33 / 33 | 25 / 25 |
| serious Total, serious adverse events | 29 / 61 | 12 / 33 | 10 / 25 |
Outcome results
Primary
Progression Free Survival
To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine in combination with AZD1775 compared to subjects receiving gemcitabine in combination with placebo. Progression is defined, using the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guideline, as at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions.
Time frame: From start of treatment until date of progression or death, whichever occurs first, up to 1 year follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Progression Free Survival | 4.6 months |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Progression Free Survival | 3.0 months |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Progression Free Survival | 5.3 months |
Secondary
Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment
To evaluate the safety and tolerability of the combination of gemcitabine combined with AZD1775 in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.
Time frame: From start of treatment until AE resolution, stabilization, or improvement to less than grade 2, up to 1 year follow-up
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Rash Maculo-Papular | 4 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Skin Infection | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Decreased White Blood Cell Count | 33 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Diarrhea | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Urinary Tract Infection | 4 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Thrombocytopenia | 19 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Aspartate Aminotransferase Increased | 3 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Weight Gain | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hematoma | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Alanine Aminotransferase Increased | 2 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Dehydration | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Decreased Lymphocyte Count | 21 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Thromboembolic Event | 2 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypokalemia | 6 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Neutropenia | 38 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypertension | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hyponatremia | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Atrial Fibrillation | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pneumonitis | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypophosphatemia | 3 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Febrile Neutropenia | 7 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Dyspnea | 3 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Enterocolitis Infection | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Anaphylaxis | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Abdominal Pain | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Fatigue | 10 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Syncope | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Nausea | 2 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pneumonia | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Headache | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Vomiting | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Fever | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pruritis | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Edema Trunk | 2 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Anemia | 19 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Alkaline Phosphatase Increased | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Catheter Related Infection | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Lung Infection | 0 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypoalbuminemia | 1 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Sepsis | 3 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Wound Complication | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Alanine Aminotransferase Increased | 2 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Enterocolitis Infection | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Neutropenia | 10 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Thrombocytopenia | 2 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Fatigue | 3 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Anemia | 6 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Decreased White Blood Cell Count | 6 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Decreased Lymphocyte Count | 6 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Febrile Neutropenia | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Abdominal Pain | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Nausea | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Vomiting | 2 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Edema Trunk | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Catheter Related Infection | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Sepsis | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Skin Infection | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Urinary Tract Infection | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Weight Gain | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Dehydration | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypokalemia | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hyponatremia | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypophosphatemia | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Dyspnea | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pneumonitis | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypertension | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Thromboembolic Event | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Aspartate Aminotransferase Increased | 3 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Diarrhea | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Rash Maculo-Papular | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypoalbuminemia | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Alkaline Phosphatase Increased | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pruritis | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Headache | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Syncope | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Anaphylaxis | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Atrial Fibrillation | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pneumonia | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hematoma | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Wound Complication | 1 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Fever | 0 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Lung Infection | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Decreased White Blood Cell Count | 16 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Diarrhea | 1 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Sepsis | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Enterocolitis Infection | 1 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Rash Maculo-Papular | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Catheter Related Infection | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hematoma | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypoalbuminemia | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Edema Trunk | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Anemia | 8 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Alkaline Phosphatase Increased | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Vomiting | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Neutropenia | 18 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pruritis | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Nausea | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Wound Complication | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Headache | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Abdominal Pain | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Fatigue | 4 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Syncope | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Febrile Neutropenia | 2 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Lung Infection | 1 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypophosphatemia | 2 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Decreased Lymphocyte Count | 9 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Anaphylaxis | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hyponatremia | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Fever | 1 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pneumonitis | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypokalemia | 2 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Atrial Fibrillation | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Hypertension | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Dehydration | 2 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Thrombocytopenia | 9 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Thromboembolic Event | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Weight Gain | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Dyspnea | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Alanine Aminotransferase Increased | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Urinary Tract Infection | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Pneumonia | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Aspartate Aminotransferase Increased | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment | Skin Infection | 0 Participants |
Secondary
Objective Response
To evaluate the objective response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) of patients receiving gemcitabine combined with AZD1775 compared to patients receiving gemcitabine in combination with placebo. RECIST v1.1 criteria used for evaluation of target lesions: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), at least a 20% increase in the sum of the diameters of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The Best Overall Response is the best response recorded from the start of the treatment until disease progression/recurrence .
Time frame: From start of treatment, every 6-8 weeks, until time of progression or death, whichever occurs first, up to 1 year follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Objective Response | 14 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Objective Response | 2 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Objective Response | 3 Participants |
Secondary
Overall Survival
To evaluate the overall survival of patients receiving gemcitabine combined with AZD1775 compared to patients receiving gemcitabine in combination with placebo.
Time frame: From start of study treatment, every 12 weeks, until death, up to 22 months follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Overall Survival | 11.4 months |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Overall Survival | 7.2 months |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Overall Survival | 13 months |
Secondary
p53 Protein Expression
To evaluate p53 protein expression by immunohistochemistry as potential predictive factors of benefit (defined as response or PFS prolongation) to AZD1775 and gemcitabine treatment. Evaluating p53 expression in patients with high-grade serous ovarian cancer and in patients with high-grade serous ovarian cancer with TP53 mutations.
Time frame: Baseline
Population: As per protocol, p53 protein expression was evaluated by immunohistochemistry to correlate with patients' mutational status of TP53
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | p53 Protein Expression | 82 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | p53 Protein Expression | 68 Participants |
Secondary
Response According to CA125 Criteria
To evaluate the GCIG CA125 response rate of patients receiving gemcitabine combined with AZD1775 compared to patients receiving gemcitabine in combination with placebo. A response according to CA-125 has occurred if there is at least a 50% reduction in CA-125 levels from a pre-treatment sample. The response must be confirmed and maintained for at least 28 days.
Time frame: From start of treatment, every 4 weeks, until time of progression or death, whichever occurs first, up to 1 year follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Response According to CA125 Criteria | 14 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Response According to CA125 Criteria | 3 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Response According to CA125 Criteria | 4 Participants |
Secondary
TP53 Mutations
To evaluate TP53 mutations (presence of mutation and type of mutation) as potential predictive factors of benefit (defined as response or PFS prolongation) to AZD1775 and gemcitabine treatment. TP53 status was assessed using Sanger sequencing.
Time frame: Baseline
Population: TP53 status was assessed in 108 patients. 8 patients had insufficient or unavailable samples and 3 patients were not tested.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | TP53 Mutations | 48 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | TP53 Mutations | 22 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | TP53 Mutations | 8 Participants |
Other Pre-specified
Change in Levels of Circulating Deoxyribonucleic Acid TP53 Mutations by TAm-Seq
Levels of circulating deoxyribonucleic acid TP53 mutations will be correlated with response. \*No results for this outcome measure
Time frame: Baseline to up to 1 year
Other Pre-specified
Changes in gH2AX in Skin and Tumor Tissue
Validation of gH2AX as a pharmacodynamic marker of therapy. \*No results for this outcome measure
Time frame: Baseline and at day 2 or 9 (course 1)
Other Pre-specified
Changes in pCDC2
Changes in pCDC2 will be correlated with survival outcomes and response rate. \*No results for this outcome measure
Time frame: Baseline and at day 2 or 9 (course 1)
Other Pre-specified
Changes in pCDC2 in Skin and Tumor Tissue
Validation of pCDC2 as a pharmacodynamic marker of therapy. \*No results for this outcome measure
Time frame: Baseline and at day 2 or 9 (course 1)
Other Pre-specified
Changes in pH2AX
Changes in pH2AX will be correlated with survival outcomes and response rate. \*No results for this outcome measure
Time frame: Baseline and at day 2 or 9 (course 1)
Other Pre-specified
Patient Reported Outcomes
Will be assessed using Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE). Each symptomatic AE is assessed with respect to 1 to 3 of the following attributes: frequency (F), severity (S) and/or interference (I) with usual or daily activities, and a recall period of 'the past 7 days'. PRO-CTCAE responses are scored from 0 to 4 with scores of 3 and 4 corresponding to high frequency, severity and/or interference. Results show the number of patients in each arm reporting high scores (3-4) for symptomatic AEs occurring in \>30% of patients
Time frame: First 3 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Fatigue S | 16 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Fatigue I | 17 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Abdominal Pain F | 10 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Abdominal Pain S | 9 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Anxiety F | 7 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Bloating F | 10 Participants |
| Arm I (WEE1 Inhibitor AZD1775, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Bloating S | 9 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Bloating S | 3 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Abdominal Pain F | 9 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Bloating F | 5 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Abdominal Pain S | 5 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Anxiety F | 6 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Fatigue S | 6 Participants |
| Arm II (Placebo, Gemcitabine Hydrochloride) | Patient Reported Outcomes | Fatigue I | 7 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Bloating S | 1 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Fatigue I | 5 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Abdominal Pain F | 1 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Fatigue S | 4 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Anxiety F | 2 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Abdominal Pain S | 0 Participants |
| Arm III (Exploratory WEE1 Inhibitor AZD1775, Gemcitabine) | Patient Reported Outcomes | Bloating F | 1 Participants |
Other Pre-specified
TP53 Mutations in Circulating Tumor Deoxyribonucleic Acid
TP53 mutations in circulating tumor deoxyribonucleic acid will be evaluated by TAm-Seq.
Time frame: Baseline
Population: Data were not collected