Progen Pharmaceuticals Limited announced the commencement of its global phase III study investigating PI-88 as an adjuvant treatment for primary liver cancer (hepatocellular carcinoma, HCC) following curative resection with the first patient having been randomised onto the study. The study is known globally as PATHWAY (PI-88 in the adjuvant treatment of HCC). The first patient to enter the trial is from Singapore, the company said.
Dr Ronnie Poon, Ph.D, M.D, global lead investigator for PATHWAY, commented, "My colleagues and I are encouraged by the phase II data that Progen has generated for PI-88 in this challenging disease, for which there are no approved treatment options. If PATHWAY is successful, PI-88 could change the standard of care for resected liver cancer patients."
PATHWAY, a double-blinded, placebo-controlled study, has been designed to establish the efficacy and safety of PI-88 in the post resection liver cancer setting. The trial will recruit approximately 600 patients at about 65-70 hospitals in more than a dozen countries. Disease-free survival, a measure of the average length of time that patients remain free of tumour recurrence, is the primary endpoint. Upon completion of this trial, the results are expected to form the basis of global registration filings for PI-88.
Justus Homburg, CEO, Progen, said, "Commencement of this trial represents a significant milestone for Progen. We have designed this trial in collaboration with world experts in this field of medicine, and with USA FDA Fast Track and EU EMEA Orphan Drug Status, its initiation underscores our commitment to making this important drug rapidly available to patients who currently have few treatment options available."
Liver cancer is one of the top five causes of cancer deaths in the world, with over half a million new cases per year. Although surgical resection is one of the few treatment options with curative potential, recurrence is common within the first 12 to 15 months following surgery and five-year survival following resection is less than 50 per cent.
Dr James Garner, vice president of Clinical and Medical Affairs, Progen said, "Since the release of our promising phase II data last year, our team has worked tirelessly to design a world-class phase III trial for PI-88 in liver cancer. We are very thankful for the support of key opinion leaders and clinicians all over the world, many of whom will now be serving as investigators in PATHWAY. While the study is starting later than we had hoped as a result of some delays opening sites due to a greater-than-expected impact from holidays over the past couple of months, Progen continues to drive aggressively country regulatory and hospital ethics approvals to conduct this phase III trial."
The study now has regulatory approval in almost half of the participating countries and more than a dozen sites have been granted approval by ethics committees. Sites are being initiated so as to be able to commence patient recruitment as soon as these necessary approvals have been granted.
PI-88 is one of a new class of multi-targeted cytostatic cancer therapeutics. It is a novel anti-cancer compound with a first-in-class mechanism as a heparan sulfate mimetic. Its anti-tumour activity is based on inhibition of two biological processes - angiogenesis (the growth of new blood vessels) and metastasis (the spread of cancer to other sites) - critical to the growth and progression of cancer. In April 2007, data from a randomised phase II trial in the post resection liver cancer setting was presented at the European Association for the Study of the Liver (EASL) meeting in Barcelona, Spain. PI-88, in this disease setting, has been granted Orphan Drug designation by the European Medicines Evaluation Agency (EMEA) and Fast Track designation by the United States Food and Drug Administration (FDA). These results provide Progen with confidence in the potential of PI-88 for this indication and we are therefore aggressively pursuing its development towards registration and commercialisation.
The phase III study investigating PI-88 as a post-resection treatment for hepatocellular carcinoma (HCC, primary liver cancer) following curative resection is a double-blinded, placebo-controlled study that has been designed to establish the efficacy and safety of PI-88 in the post-resection HCC setting. The trial will recruit approximately 600 patients at 65-70 hospitals in more than a dozen countries. Disease-free survival is the study's primary endpoint. Upon completion of this trial, the results are expected to form the basis of global regulatory filings for PI-88.