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Female Urogenital Diseases and Pregnancy Complications

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Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Peposertib

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Protein Kinase Inhibitors

Patients receive peposertib PO BID on days 1-21, days 1-28, or days 1-7 (depending on dose level) and pegylated liposomal doxorubicin hydrochloride IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection cycle 1 weeks 1 and 3. Patients also undergo CT scan or MRI during screening and every 8 weeks and after 6 months of study treatment, every 12 weeks. Patients undergo ECHO during screening and every 6 months. Starting in cycle 13, patients undergo ECHO or MUGA scan every 2 cycles.

Biospecimen Collection

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Multigated Acquisition Scan

Pegylated Liposomal Doxorubicin Hydrochloride

Site Public Contact

Bradley R. Corr

Kristen Starbuck

Panagiotis A. Konstantinopoulos

Rachel N. Grisham

Kristin L. Bixel

Kathleen N. Moore

Sarah E. Taylor

Linda R. Duska

Lisa M. Barroilhet

Rachel N Grisham

This phase I trial studies the side effects and best dose of peposertib when given together with pegylated liposomal doxorubicin hydrochloride in treating patients with high or low grade ovarian cancer that has come back after a period of improvement (recurrent). Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving peposertib and pegylated liposomal doxorubicin hydrochloride may work better in treating patients with ovarian cancer compared to pegylated liposomal doxorubicin hydrochloride alone.

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of peposertib (M3814) in combination with pegylated liposomal doxorubicin hydrochloride (PLD) and determine the recommended phase 2 dose (RP2D) of the combination in women with recurrent ovarian cancer.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To evaluate the pharmacokinetics of peposertib (M3814) when given in combination with PLD.

EXPLORATORY OBJECTIVE:

I. To correlate response to treatment (as defined by response rate and progression free survival) with PLD exposure (in area under the curve \[AUC\]) and PLD associated toxicities in women with recurrent high grade serous and low grade serous ovarian cancer treated in the expansion cohorts.

OUTLINE: This is a dose-escalation study of peposertib followed by a dose-expansion study.

Patients receive peposertib orally (PO) twice daily (BID) on days 1-21, days 1-28, or days 1-7 (depending on dose level) and pegylated liposomal doxorubicin hydrochloride intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection cycle 1 weeks 1 and 3. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) during screening and every 8 weeks throughout the study and after 6 months of study treatment, every 12 weeks. Patients undergo echocardiography (ECHO) during screening and every 6 months. Starting in cycle 13, patients undergo ECHO or multigated acquisition (MUGA) scan every 2 cycles.

After completion of study treatment, patients are followed up for 30 days.

A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer

A Phase I/Ib Dose Escalation Study of Pegylated Liposomal Doxorubicin (PLD) With Peposertib (M3814) in Platinum - Resistant or Ineligible Ovarian and Related Cancers With Planned Expansions in High Grade Serous (HGSOC) and Low Grade Serous Ovarian Cancer (LGSOC)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Tumor response will be defined according to Response Evaluation Criteria in Solid Tumors 1.1 and refers to the best overall response occurring.

Will be estimated using Kaplan-Meier method.

The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be utilized for adverse event reporting.

Individual PK parameters will be estimated for maximum of concentration, area under the curve, T1/2, apparent clearance/oral bioavailability, and apparent volume using non-compartmental methods. The PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) calculated for each dose level. Pharmacokinetic parameters will be reported descriptively for exploratory comparison with historical data. Samples from the expansion phase may also be analyzed for M3814 for the purpose of population-PK analyses.

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for endometrial high grade endometrioid adenocarcinoma