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Endometrial High Grade Endometrioid AdenocarcinomaPhase 1NCT04092270

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 1 study testing Biospecimen Collection, Computed Tomography and Echocardiography Test in people with Endometrial High Grade Endometrioid Adenocarcinoma and Fallopian Tube Clear Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Biospecimen Collection, Computed Tomography and Echocardiography Test
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
11 sitesUnited States
Study dates
7 May 2020to 8 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
  • Alkaline phosphatase =< 2.5 x institutional ULN
  • Creatinine clearance > 30 ml/min
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. The patient must be off steroids and clinically stable
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • The effects of peposertib (M3814) and liposomal doxorubicin on the developing human fetus are unknown and there is the potential for teratogenic or abortifacient effects. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 6 months after completion of peposertib (M3814) administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814), breastfeeding should be discontinued if the mother is treated with peposertib (M3814)
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
  • Archival formalin-fixed paraffin-embedded (FFPE) tissue collected within the past 36 months prior to registration must be available for submission for deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) analysis

Who cannot join

  • 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
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  • 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)
  • Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because peposertib (M3814) is DNA-PK inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814), breastfeeding should be discontinued if the mother is treated with peposertib (M3814). These potential risks may also apply to other agents used in this study
  • Patients with significant (uncontrolled) cardiac conduction abnormalities are excluded

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

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

EXPLORATORY OBJECTIVE:

  1. 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 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. Additionally, patients undergo blood sample collection throughout the study.

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

Being tested
Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging, Multigated Acquisition Scan
Medical subject headings
Neoplasms, Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • Pegylated Liposomal Doxorubicin HydrochlorideDrug

    Also called ATI-0918, Caelyx, Dox-SL, Doxil

    Given IV

  • PeposertibDrug

    Also called 3-Pyridazinemethanol, alpha-(2-Chloro-4-fluoro-5-(7-(4-morpholinyl)-4-quinazolinyl)phenyl)-6-methoxy-, (alphaS)-, M 3814, M-3814, M3814

    Given PO

Study groups in NCT04092270
Study groupRoleWhat they receive
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.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Peposertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 3 years

Secondary outcomes (1)

  1. Pharmacokinetics (PK) parameters of peposertib

    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.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2019
  2. Study start7 May 2020
  3. Primary completion12 Feb 2026
  4. Study completion8 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04092270
Sponsor's protocol ID
NCI-2019-06123
Other IDs
NCI-2019-06123, 10324, 10324, UM1CA186691
Status last verified
Jul 2026
First submitted
16 Sep 2019
Last updated
20 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Computed Tomography and Echocardiography Test in people with Endometrial High Grade Endometrioid Adenocarcinoma and Fallopian Tube Clear Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04092270.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.

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