p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246
Condition: High-grade Serous Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: APR-246; Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Intervention description: Intravenous infusion; Intravenous infusion
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer; Ovarian Carcinoma; High Grade Serous Ovarian Cancer; Recurrent Cancer; Resistant Cancer

Summary:

      The purpose of this study is to make a preliminary assessment of the efficacy of a combined
      APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade
      serous ovarian cancer (HGSOC) with mutated TP53. In addition, the study aims to assess the
      safety profile of the combined APR-246 and PLD chemotherapy regimen, to evaluate potential
      biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial
      will enroll at least 25 evaluable patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed High Grade Serous Ovarian Cancer, and positive nuclear immunohistochemical
             (IHC) staining for p53

          -  Disease Progression between 4 weeks - 6 months after the last platinum-based treatment
             was administered

          -  At least a single measurable lesion

          -  Adequate organ function prior to registration

          -  Toxicities from previous cancer therapies (excluding alopecia) must have recovered to
             grade 1 (defined by National Cancer Institute [NCI] Common Terminology Criteria for
             Adverse Events [CTCAE] version 4.0). Chronic stable grade 2 peripheral neuropathy
             secondary to neurotoxicity from prior therapies may be considered on a case by case
             basis

          -  ECOG performance status of 0 to 2

        Exclusion Criteria:

          -  Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2

          -  Hypersensitivity to PLD or to any of the excipients

          -  Unable to undergo imaging by either CT scan or MRI

          -  Evidence of any other medical conditions (such as psychiatric illness, infectious
             diseases, neurological conditions, physical examination or laboratory findings) that
             may interfere with the planned treatment, affect patient compliance or place the
             patient at high risk from treatment related complications

          -  Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma
             in situ)

          -  Is taking concurrent (or within 4 weeks prior to registration) chemotherapy,
             immunotherapy, radiotherapy, or any ancillary therapy that is considered to be
             investigational (i.e., used for non-approved indications(s) and in the context of a
             research investigation). Supportive care measures are allowed. Palliative limited
             radiation therapy for pain reduction is allowed