p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246

Aprea Therapeutics

Status and phase: Completed; Phase 2

Conditions: High-grade Serous Ovarian Cancer

Treatments: Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD); Drug: APR-246

Study type: Interventional

Funder types: Industry

Identifiers

NCT03268382

APR-486

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

APR-246 + PLD

Experimental group

Treatment:

Drug: APR-246

Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD)