Dose-Escalation Study of TH-302 in Combination With Doxorubicin to Treat Patients With Advanced Soft Tissue Sarcoma

Phase 1

Completed

• Conditions: Soft Tissue Sarcoma
• Interventions: Drug: TH-302

• Registration Number: NCT00742963
• Lead Sponsor: ImmunoGenesis

Brief Summary

The purpose of this study is to determine whether TH-302 in combination with Doxorubicin is safe and effective in the treatment of Advanced Soft Tissue Sarcoma.

Detailed Description

A broad range of tumors have been shown to contain significant numbers of hypoxic cells and hypoxia has been shown to be associated with a poor prognosis and an increase in resistance to chemotherapy and radiotherapy (Brizel 1997, Vaupel 2007, Shannon 2003).

It is likely that an agent that could effectively target hypoxic regions in tumors would improve efficacy when combined with standard chemotherapy or radiotherapy. TH-302 is activated at lower oxygen concentrations than other bioreductive prodrugs (Duan 2008) and tirapazamine, a hypoxic cytotoxin that has been extensively studied in both preclinical and clinical studies. This should result in an improved therapeutic ratio (tumor vs normal tissue toxicity) as compared with other bioreductive agents. Because TH-302 is expected to be minimally toxic to aerobic cancer cells, optimal efficacy would be expected when TH-302 is combined with treatments that are most effective under aerobic conditions such as radiotherapy and cytotoxic chemotherapy. Preclinical data have shown at least additive efficacy when TH-302 is combined with chemotherapy. In order to minimize the risk of additive toxicity, TH-302 is not being evaluated in combination with alkylating agents. The study will enroll subjects with advanced soft tissue sarcoma. These tumors have evidence supporting the presence of hypoxia based on pO2 histography, F-MISO and gene expression profiling (Vaupel 2007, Francis 2007, Rajendran 2003).

Study Timeline

• Study Start: 2008-08
• Study First Submitted: 2008-08-26
• Study First Submitted QC: 2008-08-26
• Study First Posted: 2008-08-28
• Primary Completion: 2013-07
• Study Completion: 2013-10
• Results First Submitted: 2017-07-14
• Results First Submitted QC: 2017-08-23
• Results First Posted: 2017-09-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	TH-302	75 mg/m2 of Doxorubicin administered by bolus injection starting on Day 1 of a 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) Measured of TH-302 When Used in Combination With Doxorubicin and Prophylactic Growth Factor Support in Subjects With Advanced Soft Tissue Sarcoma	Two years

Trial Locations

Locations (9)

Sarcoma Oncology Center; 🇺🇸 Santa Monica, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Indiana University Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Washingon University Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Mary Crowley Cancer Research Centers; 🇺🇸 Dallas, Texas, United States

Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States