A Study of Adavosertib (MK-1775) in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004)
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: adavosertib; Placebo; paclitaxel; carboplatin
Intervention description: Adavosertib capsules, orally, twice a day (BID) for a total of 5 doses starting on Day 1 of each 3-week cycle; placebo to adavosertib, capsule, orally, BID for a total of 5 doses, starting on Day 1 of each 3-week cycle; paclitaxel, intravenous (IV) infusion on Day 1 of each 3-week cycle; carboplatin, IV infusion on Day 1 of each 3-week cycle
Intervention MeSH terms: Paclitaxel; Carboplatin; Adavosertib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 136.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study of the safety and efficacy of adavosertib in combination with paclitaxel plus
      carboplatin in the treatment of ovarian, fallopian tube, and primary peritoneal tumors with
      the P53 mutation. In Part 1, a small group of participants will receive adavosertib along
      with paclitaxel plus carboplatin to establish the tolerability of adavosertib with this
      combination. In Part 2, participants will be randomly assigned to receive either adavosertib
      plus paclitaxel and carboplatin OR placebo plus paclitaxel and carboplatin to assess efficacy
      of adavosertib compared to placebo. The primary hypothesis of the study (Part 2) is that
      administration of adavosertib in combination with paclitaxel plus carboplatin in participants
      with platinum sensitive p53 mutant ovarian cancer will result in improvement in progression
      free survival (PFS) per enhanced Response Evaluation Criteria In Solid Tumors version 1.1
      (enhanced RECIST 1.1) compared to participants treated with paclitaxel plus carboplatin
      alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed non-low grade, non-borderline (low malignant potential)
             ovarian, fallopian tube, or primary peritoneal cancer which has progressed after
             paclitaxel / platinum-based therapy.

          -  Platinum-sensitive disease. Radiological progression must have occurred 6 months or
             more after the completion of the most recent platinum-based treatment.

          -  Measurable disease.

          -  Available tumor sample(s).

          -  Performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance
             Scale.

          -  Adequate organ function.

        Exclusion Criteria:

          -  Pregnancy or the intention to become pregnant during the course of the study.

          -  Participation in a study with an investigational compound or device within 28 days of
             receiving first dose of study medication.

          -  Active central nervous system (CNS) metastases and/or carcinomatous meningitis.

          -  Primary CNS tumor.

          -  Known hypersensitivity or contraindications to the components of potential study
             therapy (paclitaxel, carboplatin, adavosertib) or its analogs (i.e., cremophor,
             mannitol, etc.).

          -  Participant requires the use of medications or products that are metabolized by, or
             inhibit, or induce Cytochrome P450 3A (CYP3A4).

          -  Ongoing peripheral neuropathies ≥Grade 2 and related to previous treatment.

          -  Known psychiatric or substance abuse disorders.

          -  Regular use (including "recreational use") of any illicit drugs or recent history
             (within the last year) of drug or alcohol abuse.

          -  HIV positive.

          -  Active Hepatitis B or C.

          -  Symptomatic ascites or pleural effusion.

          -  Clinical history suggestive of Li Fraumeni Syndrome.