NCT03802071

A Study of Durvalumab in Combination With Doxorubicin for Advanced Soft Tissue Sarcoma

A Phase I/II Study of Durvalumab in Combination With Standard Chemotherapy Doxorubicin for Advanced Soft Tissue Sarcoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sponsor: Yonsei University · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

The yearly incidence of soft-tissue sarcomas (STS) in the USA is roughly 11,280 cases, and metastatic STS have a median overall survival of about 12 months. Sarcomas of the soft tissue are a heterogeneous group of malignant tumors of mesenchymal origin that originate in connective tissue. Local control with wide surgical resection with or without adjuvant radiation has a success rate of close to 90%. However, approximately 40% to 50% of patients with a large (\>5 cm), deep, high-grade soft-tissue sarcoma eventually develop distant metastases, primarily in the lung. Therefore, overall survival of metastatic STS remained still poor, less than 1 year. Therefore, current clinical trials with various targeted agents are ongoing add on the doxorubicin monotherapy. Investigator planned to conduct the phase I/II trial of durvalumab in combination with standard chemotherapy, doxorubicin for metastatic/recurred sofe tissue sarcoma.

Detailed description

The yearly incidence of soft-tissue sarcomas (STS) in the USA is roughly 11,280 cases, and metastatic STS have a median overall survival of about 12 months. Sarcomas of the soft tissue are a heterogeneous group of malignant tumors of mesenchymal origin that originate in connective tissue. Local control with wide surgical resection with or without adjuvant radiation has a success rate of close to 90%. However, approximately 40% to 50% of patients with a large (\>5 cm), deep, high-grade soft-tissue sarcoma (STS) eventually develop distant metastases, primarily in the lung. Therefore, overall survival (OS) of metastatic STS remained still poor, less than 1 year. Therefore, current clinical trials with various targeted agents are ongoing add on the doxorubicin monotherapy. Durvalumab (MEDI4736) is a human monoclonal antibody that inhibits binding of PD-L1. For this orphan tumor, STS, PD-L1 may be a promising strategy and favorable toxicity may warrant further combination. For this orphan tumor, STS, PD-L1 targeting may be a promising strategy and favorable toxicity may warrant further combination. Regarding anti-PD-L1 treatment in STS, in phase I trial with human monoclonal antibody to PD-L1, MPDL3280A, one heavily treated synovial sarcoma patients demonstrated partial responses. In recent phase II study of pembrolizumab, PD-1 inhibitor in advanced STS among the 40 STS cases (17.5%) had responses (1 complete response and 6 partial response). Based on the study, pembrolizumab monotherapy was approved for previously treated STS in Korea. Therefore, various clinical trials are ongoing immune checkpoint inhibitor with PDGFR inhibitors \[axitinib for renal cell carcinoma (RCC), pazopanib for RCC and STS, Sorafenib for RCC, and liver cancer, sunitinib for RCC, gastrointestinal stromal tumor, and pancreatic cancer\].

Conditions

• Sarcoma

Interventions

Type	Name	Description
DRUG	Durvalumab+doxorubicin cobination	Durvalumab 1500mg IV Doxorubicin 75mg/m2 IV D1 Q3weeks (up to 8cycles)

Timeline

• Start date: 2019-09-16
• Primary completion: 2022-08-10
• Completion: 2022-08-10
• First posted: 2019-01-14
• Last updated: 2022-06-01

Locations

1 site across 1 country: South Korea