Drug May Offer Broad Potential to Treat Solid Tumors

TGen Clinical Research Services (TCRS) at Scottsdale Healthcare and Mayo Clinic are testing a new drug that may offer broad potential to treat solid tumors.

Clinical trials of the drug TH-302 are being conducted at TGen Clinical Research Services at Scottsdale Healthcare, a partnership of the Phoenix-based Translational Genomics Research Institute (TGen) and Scottsdale-based Scottsdale Healthcare Corp., and at Mayo Clinic in Arizona.

Dr. Glen Weiss, Director of Thoracic Oncology at TCRS at Scottsdale Healthcare, said the new drug appears promising and may be more effective and less toxic to healthy tissues than conventional drugs.

‘TH-302 is a new, novel, small molecule that is activated under a metabolic condition characteristic of cancer cells — hypoxia (lack of oxygen). The drug candidate may provide an opportunity to treat slowly dividing tumor cells within hypoxic regions that generally evade traditional chemotherapeutic agents and ultimately contribute to relapse,’ Dr. Weiss said.

Phase 1 and Phase 1/2 trials are underway to investigate the safety and activity of TH-302 in patients with advanced solid tumors. After evidence of tumor activity was observed in the Phase 1 trial in patients with advanced melanoma – both non-small cell lung cancer and small cell lung cancer – the study was expanded to further investigate TH-302 anti-tumor activity in these tumors. Both Phase 1 and 1/2 trials continue to enroll patients with other solid tumors. If successful, Phase 2 and 3 clinical trials will confirm the drug’s effectiveness on solid tumors.

In cancer, as a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. This condition is called tumor hypoxia. Several studies have shown that higher levels of tumor hypoxia correlate with poor treatment outcomes for a variety of solid tumors. It is believed that hypoxia may severely limit the curability of tumors.

TH-302 is converted selectively in the presence of hypoxia to the drug’s active form, bromo-isophosphoramide mustard, a potent DNA alkylator. TH-302 targets levels of hypoxia that are common in tumors but are rare in normal tissues – this is how selective targeting of the tumor occurs. After conversion to the active form of the drug, the more resistant hypoxic cells are exposed to high concentrations of released cytotoxic agent, which can also diffuse into the oxygenated regions of a tumor cell. The Phase 1/2 trials are investigating the safety and activity of TH-302 in combination with a number of conventional chemotherapies that are believed to be effective in the non-hypoxic regions of solid tumors.

The clinical trial at TCRS at Scottsdale Healthcare will investigate the safety and pharmacology of multiple doses of TH-302 in patients with late-stage cancer.

Release Date: January 29, 2009
Source: The Translational Genomics Research Institute