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

Undifferentiated Pleomorphic Sarcoma Clinical Trial

Official title: A Randomized Phase II Trial of Doxorubicin + Pembrolizumab Versus Doxorubicin Alone for the Treatment of Undifferentiated Pleomorphic Sarcoma (UPS) and Related Poorly Differentiated Sarcomas

Status Not yet recruiting

Clinical Trial Summary

This phase II trial compares the effect of immunotherapy (pembrolizumab) plus chemotherapy (doxorubicin) to chemotherapy (doxorubicin) alone in treating patients with undifferentiated pleomorphic sarcoma (UPS) or a related poorly differentiated sarcoma that has spread from where it first started 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 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 UPS or a related poorly differentiated sarcoma live longer without having disease progression.

Clinical Trial Description

PRIMARY OBJECTIVE:

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.

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).

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.

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 echocardiogram (ECHO) or multigated acquisition (MUGA) scan during screening, as well as standard imaging scans and blood sample collection throughout the study.

After completion of study treatment, patients are followed up periodically for up to 5 years. ;

Related Conditions & MeSH terms

• Histiocytoma, Malignant Fibrous
• Sarcoma
• Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
• Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
• Undifferentiated Pleomorphic Sarcoma

• NCT number: NCT06422806
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 14, 2024
• Completion date: June 30, 2026