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)
3 other identifiers
interventional
54
1 country
11
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2020
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 16, 2019
CompletedFirst Posted
Study publicly available on registry
September 17, 2019
CompletedStudy Start
First participant enrolled
May 7, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
April 17, 2026
April 1, 2026
6.1 years
September 16, 2019
April 16, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events
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.
Up to 3 years
Secondary Outcomes (1)
Pharmacokinetics (PK) parameters of nedisertib
Up to 3 years
Other Outcomes (3)
Tumor response
Within the first 10 months of treatment
Duration of response
From response documentation until progression of disease, assessed up to 3 years
Progression-free survival
From the beginning of the treatment until the progression date, death date, or the last radiological assessment without progressive disease, assessed up to 3 years
Study Arms (1)
Treatment (peposertib, PLD)
EXPERIMENTALPatients 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 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. Additionally, patients undergo blood sample collection throughout the study.
Interventions
Undergo MUGA scan
Given IV
Undergo blood sample collection
Undergo ECHO
Undergo MRI
Undergo CT scan
Given PO
Eligibility Criteria
You may qualify if:
- DOSE ESCALATION PHASE: Women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer are eligible. This includes, but is not limited to, the following histologic types: serous adenocarcinoma (grade 1,2, or 3/ high grade or low grade), endometrioid adenocarcinoma, carcinosarcoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, or adenocarcinoma not otherwise specified
- NOTE: Patients who have evidence of DDR deficiency /HRD are eligible if they are at the point in their disease course where they are appropriate candidates for single agent Doxil
- EXPANSION PHASE: The expansion phase will simultaneously accrue to 2 cohorts, low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC)
- Patients accrued to the LGSOC cohort will have recurrent or persistent low grade serous ovarian cancer or grade 1 serous ovarian cancer
- Patients accrued to the HGSOC cohort will have recurrent or persistent high grade serous ovarian cancer
- Patients must have measurable disease by defined Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- Prior therapy:
- Patients must have received at least one prior line of platinum-based chemotherapy
- Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
- Any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted therapy, immunotherapy, or hormonal therapy must be discontinued at least 4 weeks, one cycle, or 5 half-lives (whichever is shortest) prior to study treatment initiation
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with pegylated liposomal doxorubicin in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Patients with platinum-sensitive ovarian cancer are eligible for only the dose expansion phase if their provider feels that PLD would be an appropriate treatment option for them. Patients with platinum-sensitive ovarian cancer should also be offered any higher priority studies for which they are potentially eligible and/or platinum based chemotherapy or a PARP inhibitor if they are eligible for such therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Patients must have a cardiac ejection fraction \>= the institutional lower limit of normal (LLN)
- Hemoglobin \>= 9 g/dL
- +16 more criteria
You may not qualify if:
- Patients are excluded from the dose-escalation phase of the study if they are eligible for any available therapies known to confer clinical benefit
- Inability to swallow and/or absorb oral medication (patients with a drainage peg are ineligible)
- Patients may not have received prior anthracyclines (doxorubicin or pegylated liposomal doxorubicin) for treatment of their ovarian cancer
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia, thyroid dysfunction, or neuropathy
- Patients who are receiving any other investigational agents within 28 days prior to start of treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) or pegylated liposomal doxorubicin
- Patients who cannot discontinue concomitant medications or herbal supplements that potentially interact with peposertib (M3814)
- The following categories of medications and herbal supplements must be discontinued prior to starting study treatment:
- Strong inducers/inhibitors of CYP3A4/5, CYP2C9, and CYP2C19
- Substrates with a narrow therapeutic index that are metabolized by CYP1A2, 2B6, 2C8, and 3A4/5
- Use caution with other substrates of CYP3A4/5, CYP1A2, CYP2B6, CYP2C8 and substrates of P-gp, BCRP, OCT1, OAT3, OATP1B1, OATP1B3, MATE1, and MATE-2K with a narrow therapeutic index. Close monitoring is advised
- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Patient Drug Interactions Handout and Wallet Card) should be provided to patients
- Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued \>= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
- Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
- Patients who have received a live attenuated vaccine within 30 days of dosing with peposertib (M3814)
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rachel N Grisham
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 16, 2019
First Posted
September 17, 2019
Study Start
May 7, 2020
Primary Completion (Estimated)
June 1, 2026
Study Completion (Estimated)
June 1, 2026
Last Updated
April 17, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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.