TopoTarget A/S and CuraGen Corporation has announced that the initiation of patient dosing in a phase I/II clinical trial evaluating the safety and potential efficacy of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of inoperable hepatocellular cancer. This trial is being sponsored by the National Cancer Institute (NCI) under a clinical trials agreement, with CuraGen for PXD101. This phase I/II trial is an open-label study being led by Dr Winnie Yeo at the Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital in Shatin, Hong Kong.
The phase I portion of the study aims to establish the maximum tolerated dose (MTD), pharmacokinetics, and safety profile of PXD101 for patients with inoperable hepatocellular cancer. Approximately 15 patients will be enrolled in the dose escalation portion of the study and receive PXD101 in continuous three week cycles until disease progression.
Determination of the MTD, the phase II portion of the trial, will be initiated and enrol up to 29 additional patients to assess the safety and potential efficacy of PXD101. Assessment of tumour response will be evaluated using the RECIST criteria. Secondary pharmacological studies evaluating histone acetylation, induction of cell-cycle arrest or apoptosis, and changes in gene expression will be conducted in a subset of enrolled patients.
Dr Yeo, Principal Investigator, commented "We are pleased with yet another clinical trial with PXD101 being initiated. Hepatocellular carcinoma, also known as liver cancer, is an aggressive form of cancer that has limited treatment options for those patients who have inoperable disease. Preclinical research suggests that HDAC inhibitors, such as PXD101, have activity against hepatocellular carcinoma cell lines, potentially restoring normal gene expression and causing cancer cell death. Therefore, we are very excited to begin this trial and learn more about the safety and potential activity of PXD101 in the treatment of this disease." The initiation of this trial does not change TopoTarget's financial expectations for full-year 2006.
PXD101 is a promising small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid and haematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents, including 5-fluorouracil (5-FU), carboplatin, paclitaxel, Velcade (bortezomib) and cis-retinoid acid for injection.