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

ConditionsMetastatic Dedifferentiated LiposarcomaMetastatic LeiomyosarcomaMetastatic MyxofibrosarcomaMetastatic SarcomaMetastatic Synovial SarcomaMetastatic Undifferentiated Pleomorphic SarcomaUnresectable Dedifferentiated LiposarcomaUnresectable LeiomyosarcomaUnresectable MyxofibrosarcomaUnresectable SarcomaUnresectable Synovial SarcomaUnresectable Undifferentiated Pleomorphic Sarcoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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/m²

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tissue biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Pegylated Liposomal Doxorubicin Hydrochloride

    Drug

    Given IV

  • Peposertib

    Drug

    Given PO

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: Treatment (peposertib, liposomal doxorubicin)Experimental treatment 8 interventions

Trial outcomes

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.

Time frame
Up to 28 days

Secondary outcomes

1

Incidence of adverse events

AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.

Time frame
Up to 30 days after the end of study treatment
2

Objective response rate

Assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

Time frame
Up to 28 days
3

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.

Time frame
From study enrollment until disease progression (determined by RECIST v1.1) or death due to any cause, whichever occurs first
4

Homologous recombination deficiency (HRD) status

Will be defined by HRD score and mutational signature analysis.

Time frame
Up to 1 year

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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