Metastatic Dedifferentiated LiposarcomaPhase 1NCT05711615
Testing Low-Dose Common Chemotherapy (Liposomal Doxorubicin) in Combination With an Anti-Cancer Drug, Peposertib, in Advanced Sarcoma
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Dedifferentiated Liposarcoma and Metastatic Leiomyosarcoma, run by National Cancer Institute (NCI) at 16 sites in United States.
Trial summary
This phase I trial tests the safety, side effects, and best dose of combination therapy with liposomal doxorubicin and peposertib in treating patients with sarcoma that has spread from where it first started, to other places in the body (metastatic), or cannot be removed by surgery (unresectable) and for which no… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Dedifferentiated Liposarcoma, Metastatic Leiomyosarcoma, Metastatic Myxofibrosarcoma
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 16 sitesUnited States
- Study dates
- 6 Feb 2024to 3 Nov 2026
- Phase
- Phase 1
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed sarcoma that is metastatic or unresectable and for which there is no known curative treatment
- Patients must have histologic diagnosis of leiomyosarcoma (LMS) or selected soft tissue sarcomas (myxofibrosarcoma [MFS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma, or dedifferentiated liposarcoma [DDLPS]). Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study. If the pathology has previously been reviewed by another site participating in the study, the diagnosis does not need to be re-reviewed at the enrolling site
- Patients must have evaluable disease that is amenable to biopsy
- Patients must have been treated with at least 1 prior line of therapy. Prior anthracycline use is permitted as long as the cumulative dose prior to enrollment does not exceed 360 mg/m^2
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with liposomal doxorubicin in patients < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
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- 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
- Hemoglobin >= 8 g/dL
- Glomerular filtration rate (GFR) >= 51 mL/min/1.73 m^2 (per institutional estimate based on creatinine level)
- 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 and clinical symptoms are stable while off steroid support
- 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 of clinically significant cardiac disease, 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
- 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
- Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 3 months after the last dose of peposertib (M3814) and 6 months after the last dose of liposomal doxorubicin
- Male patients of reproductive potential must agree to avoid impregnating a partner while receiving study drug and for 3 months after the last dose of peposertib (M3814) and 6 months after the last dose of liposomal doxorubicin by complying with adequate methods of contraception
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
- 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
Who cannot join
- 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
- Prior palliative radiotherapy within 14 days of cycle 1 day 1 and prior definitive radiotherapy within 42 days of cycle 1 day 1. Adverse effects of radiation therapy must resolve to baseline prior to cycle 1 day 1
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) or other agents used in study
- Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9, and CYP2C19. Participants who cannot discontinue substrates with a narrow therapeutic index that are metabolized by CYP1A2, CYP2B6, CYP2C8, and CYP3A4/5 are ineligible. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time before the patient can be treated:
- Strong inducers of CYP3A4/5 and CYP2C19: >= 3 weeks prior to study treatment
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- Strong inhibitors of CYP3A4/5 and CYP2C19: >= 1 week prior to study treatment
- Substrates of CYP3A4/5 with a narrow therapeutic index: >= 1 day prior to study treatment
- Strong inhibitors of CYP2C9: >= 1 week prior to study treatment
- 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 with left ventricular ejection fraction (LVEF) measurement below the institutional lower limit of normal (LLN) are excluded
- Patients with uncontrolled intercurrent illness
- Patients who cannot swallow tablets whole
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are not eligible
- Pregnant women are excluded from this study because peposertib (M3814) is an adenosine triphosphate (ATP)-competitive inhibitor of DNA-protein kinase catalytic subunit (PKcs) 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 may not have received prior treatment with a DNA-protein kinase (PK) inhibitor
Trial locations and contacts
16 sites in 1 country. Contact the study team or a site near you to ask about taking part.
16 sites in 1 country
United States16 sites, 15 recruiting
- Suspended
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
- Recruiting
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Site Public Contact, 720-848-0650
Breelyn A. Wilky
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
H. Catherine Wilbur
- Recruiting
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
Site Public Contact, 800-411-1222
A P. Chen
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Site Public Contact, 877-442-3324
Candace L. Haddox
- Recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu
Paul V. Viscuse
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Daniel J. Olson
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Site Public Contact, 866-632-6789, askmdanderson@mdanderson.org
Michael S. Nakazawa
- Recruiting
Los Angeles General Medical Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451, uscnorrisinfo@med.usc.edu
Mark Agulnik
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Mark Agulnik
- Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Site Public Contact, 305-243-2647
Emily E. Jonczak
- Recruiting
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Daniel J. Olson
- Recruiting
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Daniel J. Olson
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Melissa A. Burgess
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Mia C. Weiss
- Recruiting
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Mia C. Weiss
About this study
Official title: A Phase 1 Study of Peposertib (M3814) and Low-Dose Liposomal Doxorubicin in Patients With Metastatic Leiomyosarcoma and Other Soft Tissue Sarcomas
This phase I trial tests the safety, side effects, and best dose of combination therapy with liposomal doxorubicin and peposertib in treating patients with sarcoma that has spread from where it first started, to other places in the body (metastatic), or cannot be removed by surgery (unresectable) and for which no known cure is available (advanced). Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also enhance the activity of chemo- and radiotherapy. There is some pre-clinical evidence in animal models that combining peposertib with liposomal doxorubicin can shrink or stabilize certain types of cancer for longer than either drug alone, but it is not known if this will happen in people. Combination therapy with liposomal doxorubicin and peposertib may be effective in treating patients with advanced sarcoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability of peposertib in combination with low-dose pegylated liposomal doxorubicin hydrochloride (liposomal doxorubicin) as evaluated by the dose-limiting toxicity (DLT) rate at each tested dose level.
II. To determine the recommended phase 2 dose (RP2D) of liposomal doxorubicin and peposertib combination and determine the maximal tolerated dose (MTD) if identified.
SECONDARY OBJECTIVE:
- To assess the pharmacokinetics of peposertib and liposomal doxorubicin used in combination with each other.
CORRELATIVE OBJECTIVES:
- To test the hypothesis that soft tissue sarcomas (STS) with homologous recombination deficiency (HRD) like leiomyosarcomas (LMS) will be more susceptible to DNA-protein kinase inhibitor (PKi) in combination with low-dose liposomal doxorubicin.
II. To test the hypothesis that gammaH2AX and pNBS1 can be used as pharmacodynamic biomarkers of response to DNA-PKi in combination with low-dose liposomal doxorubicin.
III. To test the hypothesis that disease activity correlates with circulating tumor DNA levels in the plasma.
OUTLINE: This is a dose-escalation study of peposertib and liposomal doxorubicin.
Patients receive peposertib orally (PO) twice daily (BID) on days 1-28 of each cycle and liposomal doxorubicin intravenously (IV) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity or withdrawal of consent. Patients undergo blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo tissue biopsy and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and on the trial.
Patients are followed for 30 days after removal from study or until death, whichever occurs first.
- Conditions
- Metastatic Dedifferentiated Liposarcoma, Metastatic Leiomyosarcoma, Metastatic Myxofibrosarcoma, Metastatic Sarcoma, Metastatic Synovial Sarcoma, Metastatic Undifferentiated Pleomorphic Sarcoma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging
- Medical subject headings
- Liposarcoma, Leiomyosarcoma, Dermatofibrosarcoma, Sarcoma, Sarcoma, Synovial, Histiocytoma, Malignant Fibrous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tissue biopsy
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
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 group | Role | What they receive |
|---|---|---|
| Treatment (peposertib, liposomal doxorubicin) | Experimental | Patients receive peposertib PO BID on days 1-28 of each cycle and liposomal doxorubicin IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity or withdrawal of consent. Patients undergo blood sample collection and CT or MRI throughout the trial. Patients also undergo tissue biopsy and ECHO or MUGA during screening and on the trial. Receives: Procedure: Biopsy Procedure; 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.
Dose limiting toxicity (DLT) rate
The number and type of DLT seen at each dose level will be provided. The adverse events (AEs) will also be summarized by AE type and the maximum grade of the AE experienced by the patient for each dose level. DLT will be used to determine the recommended phase 2 dose of study drugs.
Measured: Up to 28 days
Secondary outcomes (5)
Incidence of adverse events
AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.
Measured: Up to 30 days after the end of study treatment
Objective response rate
Assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
Measured: Up to 28 days
Progression free survival
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. Patients who are alive at the time of analysis without a documented disease progression will be censored at the time of their last tumor evaluation.
Measured: From study enrollment until disease progression (determined by RECIST v1.1) or death due to any cause, whichever occurs first
Homologous recombination deficiency (HRD) status
Will be defined by HRD score and mutational signature analysis.
Measured: Up to 1 year
Deoxyribonucleic acid damage repair activity
Will be defined by gammaH2AX and NBS1 S343 phosphorylation based on the National Clinical Laboratory Network DDR3 assay.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2023
- Study start6 Feb 2024
- Primary completion3 Nov 2026 (estimated)
- Study completion3 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Dedifferentiated LiposarcomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Candace L Haddox, Principal investigator, Dana-Farber - Harvard Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05711615
- Sponsor's protocol ID
- NCI-2023-00574
- Other IDs
- NCI-2023-00574, 10563, 10563, UM1CA186709
- Status last verified
- Jul 2026
- First submitted
- 2 Feb 2023
- Last updated
- 22 Oct 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.