Trials / Recruiting

RecruitingNCT06422806

Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas

A Randomized Phase III Trial of Doxorubicin + Pembrolizumab Versus Doxorubicin Alone for the Treatment of Dedifferentiated Liposarcoma (DDLPS), Undifferentiated Pleomorphic Sarcoma (UPS) and Related Poorly Differentiated Sarcomas

Status: Recruiting
Phase: Phase 3
Study type: Interventional
Enrollment: 365 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase III trial compares the effect of immunotherapy (pembrolizumab) plus chemotherapy (doxorubicin) to chemotherapy (doxorubicin) alone in treating patients with dedifferentiated liposarcoma (DDLPS), undifferentiated pleomorphic sarcoma (UPS) or a related poorly differentiated sarcoma that has spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's deoxyribonucleic acid (DNA) and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding immunotherapy (pembrolizumab) to the standard chemotherapy (doxorubicin) may help patients with metastatic or unresectable DDLPS, UPS or a related poorly differentiated sarcoma live longer without having disease progression.

Detailed description

PRIMARY OBJECTIVES: I. To assess whether the combination of doxorubicin and pembrolizumab will improve progression free survival (PFS) in UPS and related poorly differentiated sarcomas relative to doxorubicin alone. II. To assess whether the combination of doxorubicin and pembrolizumab will improve PFS in DDLPS relative to doxorubicin alone. KEY SECONDARY OBJECTIVE: I. To assess whether the combination of doxorubicin and pembrolizumab versus (vs) the re-introduction of pembrolizumab in the doxorubicin alone arm at disease progression (i.e., upfront pembrolizumab vs second line pembrolizumab) improves overall survival (OS) in DDLPS and the UPS family of diseases. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability in each treatment arm. II. To quantify overall response rate (ORR) and durability of response (DOR) in each treatment. EXPLORATORY OBJECTIVES: I. To evaluate the agreement between the central review and local Response Evaluation Criteria in Solid Tumors (RECIST) assessments for patients identified for central imaging review. II. To compare PFS, OS, ORR and DOR of doxorubicin with or without pembrolizumab for all patients, combining the UPS and DDLPS patients together. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive doxorubicin intravenously (IV) over 3-10 minutes or up to 3 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive doxorubicin IV over 3-10 minutes or up to 3 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. At time of disease progression, patients may begin receiving pembrolizumab alone IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of additional progression or unacceptable toxicity. Patients in both arms also undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan, standard imaging scans and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months in years 2-10.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Diagnostic Imaging Testing	Undergo standard imaging scans
DRUG	Doxorubicin	Given IV
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA scan
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

Start date: 2024-09-11
Primary completion: 2026-06-30
Completion: 2026-06-30
First posted: 2024-05-21
Last updated: 2026-04-14

Locations

248 sites across 3 countries: United States, Canada, Puerto Rico

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06422806. Inclusion in this directory is not an endorsement.