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

Aprea Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02098343

APR-407

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 carboplatin/PLD chemotherapy regimen, compared with carboplatin/PLD chemotherapy regimen alone, in patients with platinum sensitive recurrent high grade serous ovarian cancer (HGSOC) with mutated p53. In addition, the study aims to assess the safety profile of the combined APR-246 and carboplatin/PLD chemotherapy regimen compared with carboplatin/PLD chemotherapy regimen alone, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll up to a maximum of 400 patients.

Enrollment: 247 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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247 participants in 5 patient groups

Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.

Experimental group

Description:

Dose escalation of APR-246.

Treatment:

Drug: APR-246

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Phase II: Arm A. APR-246 + Carboplatin/PLD.

Experimental group

Description:

Experimental

Treatment:

Drug: APR-246

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Phase II: Arm B. Carboplatin/PLD.

Active Comparator group

Description:

Active Comparator

Treatment:

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.

Experimental group

Description:

Dose escalation of APR-246.

Treatment:

Drug: APR-246

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.

Experimental group

Description:

Dose escalation of APR-246.

Treatment:

Drug: APR-246

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)