NCT00743379

Dose-Escalation Study of TH-302 in Combination With A) Gemcitabine or B) Docetaxel or C) Pemetrexed to Treat Advanced Solid Tumors

A Phase 1/2, Multicenter, Dose-Escalation Study to Determine the Safety, Efficacy and Pharmacokinetics of TH-302 in Combination With A) Gemcitabine or B) Docetaxel or C) Pemetrexed in Patients With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 71 (actual)
• Sponsor: Threshold Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine if TH-302, in combination with A) Gemcitabine, or B) Docetaxel or C) Pemetrexed methotrexate, are safe and effective in the treatment of Pancreatic Cancer, Castrate-resistant Prostate Cancer, and Non-small Cell Lung Cancer, respectively.

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 either docetaxel or gemcitabine. In order to minimize the risk of additive toxicity, TH-302 is not being evaluated in combination with alkylating agents.

Conditions

• Non-Small Cell Lung Cancer
• Prostate Cancer
• Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	TH-302	TH-302 will be administered by IV infusion over 30 minutes on Days 1, 8 and 15 of a 28- day cycle for Arm A and on Days 1 and 8 of a 21 day cycle for Arms B and C.

Timeline

• Start date: 2008-08-01
• Primary completion: 2013-07-01
• Completion: 2014-03-01
• First posted: 2008-08-28
• Last updated: 2015-05-07

Locations

11 sites across 1 country: United States