Testing Low-Dose Common Chemotherapy (Liposomal Doxorubicin) in Combination With an Anti-Cancer Drug, Peposertib, in Advanced Sarcoma
A Phase 1 Study of Peposertib (M3814) and Low-Dose Liposomal Doxorubicin in Patients With Metastatic Leiomyosarcoma and Other Soft Tissue Sarcomas
3 other identifiers
interventional
30
1 country
16
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Feb 2024
Typical duration for phase_1
16 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
February 2, 2023
CompletedFirst Posted
Study publicly available on registry
February 3, 2023
CompletedStudy Start
First participant enrolled
February 6, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 3, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 3, 2026
July 31, 2026
July 1, 2026
2.7 years
February 2, 2023
July 30, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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.
Up to 28 days
Secondary Outcomes (5)
Incidence of adverse events
Up to 30 days after the end of study treatment
Objective response rate
Up to 28 days
Progression free survival
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
Up to 1 year
Deoxyribonucleic acid damage repair activity
Up to 1 year
Study Arms (1)
Treatment (peposertib, liposomal doxorubicin)
EXPERIMENTALPatients 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.
Interventions
Undergo blood sample collection
Undergo CT scan
Undergo MRI
Undergo tissue biopsy
Undergo ECHO
Undergo MUGA
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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%)
- 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
- +8 more criteria
You may not qualify if:
- 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
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
UT MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Candace L Haddox
Dana-Farber - Harvard 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
February 2, 2023
First Posted
February 3, 2023
Study Start
February 6, 2024
Primary Completion (Estimated)
November 3, 2026
Study Completion (Estimated)
November 3, 2026
Last Updated
July 31, 2026
Record last verified: 2026-07
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.