RECRUITING

Testing Low-Dose Common Chemotherapy (Liposomal Doxorubicin) in Combination With an Anti-Cancer Drug, Peposertib, in Advanced Sarcoma

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Conditions

Metastatic Dedifferentiated LiposarcomaMetastatic LeiomyosarcomaMetastatic MyxofibrosarcomaMetastatic SarcomaMetastatic Synovial SarcomaMetastatic Undifferentiated Pleomorphic SarcomaUnresectable Dedifferentiated LiposarcomaUnresectable LeiomyosarcomaUnresectable MyxofibrosarcomaUnresectable SarcomaUnresectable Synovial SarcomaUnresectable Undifferentiated Pleomorphic Sarcoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1 Study of Peposertib (M3814) and Low-Dose Liposomal Doxorubicin (Doxil®) in Patients With Metastatic Leiomyosarcoma and Other Soft Tissue Sarcomas

Quick Facts

Study Start:2024-02-06
Study Completion:2025-05-03
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05711615

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Patients must have histologically confirmed sarcoma that is metastatic or unresectable and for which there is no known curative treatment
  2. * Dose escalation cohort: 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
  3. * Dose expansion cohort: Patients must have histology diagnosis of LMS. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study
  4. * Dose escalation cohort: Patients must have evaluable disease that is amenable to biopsy
  5. * Dose expansion cohort: Patients must have disease which is measurable at study entry according to RECIST 1.1 criteria and amenable to biopsy
  6. * 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 300 mg/m\^2
  7. * 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
  8. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) for both dose escalation and dose expansion
  9. * Absolute neutrophil count \>= 1,500/mcL
  10. * Platelets \>= 100,000/mcL
  11. * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
  12. * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
  13. * Hemoglobin \>= 8 g/dL
  14. * Glomerular filtration rate (GFR) \>= 51 mL/min/1.73 m\^2 (per institutional estimate based on creatinine level)
  15. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  16. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  17. * 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
  18. * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression while off steroid support
  19. * 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
  20. * 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 and have an left ventricular ejection fraction (LVEF) above the institutional upper limit of normal if LVEF measurement is available
  21. * 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
  22. * 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
  23. * 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
  24. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
  25. * Ability to understand and the willingness to sign a written informed consent document
  1. * 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
  2. * 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
  3. * Patients who are receiving any other investigational agents
  4. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) or other agents used in study
  5. * 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. Concomitant use of CYP3A4/5 substrates with a narrow therapeutic index are also excluded. 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:
  6. * Strong inducers of CYP3A4/5 and CYP2C19: \>= 3 weeks prior to study treatment
  7. * Strong inhibitors of CYP3A4/5 and CYP2C19: \>= 1 week prior to study treatment
  8. * Substrates of CYP3A4/5 with a narrow therapeutic index: \>= 1 day prior to study treatment
  9. * Strong inhibitors of CYP2C9: \>= 1 week prior to study treatment
  10. * 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
  11. * LVEF measurement and baseline electrocardiogram (ECG) should be performed as clinically indicated based on cardiac risk assessment of the investigator; patients with known LVEF \< the institutional lower limit of normal (LLN) are excluded
  12. * Patients with uncontrolled intercurrent illness
  13. * Patients who cannot swallow tablets whole
  14. * Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
  15. * 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
  16. * Patients may not have received prior treatment with a DNA-protein kinase (PK) inhibitor

Contacts and Locations

Principal Investigator

Candace L Haddox
PRINCIPAL_INVESTIGATOR
Dana-Farber - Harvard Cancer Center LAO

Study Locations (Sites)

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
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 - Harvard Cancer Center LAO
Boston, Massachusetts, 02115
United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
United States
Washington University School of Medicine
Saint Louis, Missouri, 63110
United States
Siteman Cancer Center-South County
Saint Louis, Missouri, 63129
United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
United States
M D Anderson Cancer Center
Houston, Texas, 77030
United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Candace L Haddox, PRINCIPAL_INVESTIGATOR, Dana-Farber - Harvard Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-02-06
Study Completion Date2025-05-03

Study Record Updates

Study Start Date2024-02-06
Study Completion Date2025-05-03

Terms related to this study

Additional Relevant MeSH Terms

  • Metastatic Dedifferentiated Liposarcoma
  • Metastatic Leiomyosarcoma
  • Metastatic Myxofibrosarcoma
  • Metastatic Sarcoma
  • Metastatic Synovial Sarcoma
  • Metastatic Undifferentiated Pleomorphic Sarcoma
  • Unresectable Dedifferentiated Liposarcoma
  • Unresectable Leiomyosarcoma
  • Unresectable Myxofibrosarcoma
  • Unresectable Sarcoma
  • Unresectable Synovial Sarcoma
  • Unresectable Undifferentiated Pleomorphic Sarcoma