Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Condition: Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; 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
MeSH terms: Carcinoma; Adenocarcinoma; Fallopian Tube Neoplasms; Carcinoma, Endometrioid; Carcinosarcoma; Cystadenocarcinoma; Cystadenocarcinoma, Serous; Cystadenocarcinoma, Mucinous; Brenner Tumor; Adenocarcinoma, Papillary; Recurrence
Intervention: Adavosertib; Gemcitabine Hydrochloride; Laboratory Biomarker Analysis; Pharmacological Study; Placebo Administration; Questionnaire Administration
Intervention description: Given PO; Given IV; Correlative studies; Correlative studies; Given PO; Ancillary studies
Intervention MeSH terms: Gemcitabine; Adavosertib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 124.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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