A Study Comparing Gemcitabine with or without AZD 1775 in Treating Patients with Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer


About this study

The purpose of this study is to compare gemcitabine hydrochloride in combination with AZD 1775 to gemcitabine hydrochloride given alone to treat patients with ovarian, primary peritoneal, or fallopian tube cancer that has returned 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. AZD 1775 may block specific protein activity and may increase the effectiveness of gemcitabine hydrochloride by preventing the protein from repairing damaged tumor cells without causing harm to normal cells. It is not yet known whether gemcitabine hydrochloride with or without AZD1775 may be an effective treatment for recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • 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 high grade serous ovarian cancer will be considered for the statistical analysis
  • non-high grade serous cancers will be allowed in an exploratory cohort
  • 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
    • Must have had radiological progression to that regimen
  • 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
  • No limitation in the number of prior lines of therapy
  • 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 proof 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 (T), 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
  • Must be able to tolerate oral medication and not have evidence of active bowel obstruction
    • Can have a history of prior bowel obstruction, provided is not having symptoms of bowel obstruction at the time of enrollment and the bowel obstruction is not anticipated to recur during the participation in the study
  • 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
    • If a woman becomes pregnant or suspects 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
      • Have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
      • Are not postmenopausal
        • postmenopause is defined as amenorrhea ≥ 12 consecutive months
        • 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

  • Previously received gemcitabine for the treatment of recurrent disease
  • Are receiving any other investigational agents
  • Have clinically or radiologically unstable brain metastases
    • 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
  • Are taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice)
    • 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
      • 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
  • Human immunodeficiency virus (HIV)-positive on combination antiretroviral therapy
  • 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 
    • Cerebrovascular disease with previous stroke
    • Psychiatric illness/social situations that would limit compliance with study requirements

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Andrea Wahner Hendrickson, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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