p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

Inclusion Criteria:

- Confirmed High Grade Serous Ovarian Cancer, and positive nuclear immunohistochemical
(IHC) staining for p53

- Disease Progression between 6-24 months after a first or second platinum based regimen

- At least a single measurable lesion. Phase II patients only

- Adequate organ function prior to registration

- Toxicities from previous cancer therapies must have recovered to grade 1 (defined by
Common Terminology Criteria for Adverse Events [CTCAE] 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 1

Exclusion Criteria:

- Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2

- History of allergic reactions to carboplatin, platinum containing compounds or
mannitol and/or 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 week 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