Biomira Inc has announced that the phase II clinical trial of PX-12 in patients with advanced pancreatic cancer is open for enrolment.

PX-12 is a proprietary small molecule designed to inhibit the activity of thioredoxin (Trx-1), a protein that regulates a number of cancer-related pathways. Biomira anticipates that the first patient in the trial will be treated in January 2007.

The randomised, open-label phase II trial will evaluate two dose levels of PX-12 in patients with advanced pancreatic cancer whose tumours have progressed while being treated with gemcitabine or gemcitabine-containing regimens. Up to 80 patients are expected to be enrolled in the trial at three centres in the United States: the Virginia G. Piper Cancer Centre in Scottsdale, Arizona; the University of Arizona Cancer Centre, Tucson; and the University of Texas MD Anderson Cancer Centre in Houston.

The United States National Cancer Institute (NCI) is partially funding the trial under a Clinical Trials Agreement with the Translational Genomics Research Institute (TGen). The principal investigator for the trial is Daniel D. Von Hoff, MD.

"Trx-1 is known to control diverse molecular pathways that contribute to the growth, survival and drug resistance of many cancers," said D Lynn Kirkpatrick, PhD, Biomira's chief scientific officer. "By inhibiting Trx-1, PX-12 may have utility in a variety of cancer indications, including pancreatic cancer, an aggressive malignancy for which there are limited treatment options and significant unmet medical needs."

PX-12 is an irreversible inhibitor of thioredoxin (Trx-1), a protein that regulates many transcription factors including hypoxia inducible factor (HIF)-1 alpha, vascular endothelial growth factor (VEGF) and activator protein 1 (AP-1). These factors play a critical role in cancer cell growth, survival and resistance to chemotherapy. Increased thioredoxin levels in cancer cells have been linked to the aggressive proliferation of solid tumours, including colon, lung, and gastric cancers. PX-12 has successfully completed phase I safety evaluation and is currently being studied in a phase IB trial for the treatment of gastrointestinal cancers. An initial phase I trial involving 38 patients with advanced metastatic cancer showed that PX-12 was well tolerated and produced a decrease in plasma concentrations of thioredoxin that was significantly correlated with increased patient survival. Seven of the 38 patients achieved stable disease of up to 322 days.