CuraGen Corporation and TopoTarget A/S has announced that the initiation of a phase I clinical trial, evaluating the administration of oral PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumours. The phase I trial will be led by Dr W. Kevin Kelly, Associate Prof. of Medicine in the Section of Medical Oncology and head of The Prostate and Urologic Oncology Programme at the Yale Cancer Centre, New Haven, CT.
The phase I study is an open-label, multi-centre trial designed to establish the maximum tolerated dose (MTD) for oral PXD101 administered once or twice daily. Patients will be treated with oral PXD101 in a dose-escalation regimen and may continue to receive up to eight or more treatment cycles depending on disease response. Primary objectives for the study include evaluation of the safety, tolerability and pharmacokinetics of oral PXD101. Secondary objectives include assessment of the pharmacokinetic profile of oral PXD101 administered once or twice daily at various dose levels and evaluation of anti-tumour activity. The study is being conducted at sites both in the US and Europe, with preliminary results expected to be available by the end of 2007.
"We believe that the availability of both an oral and intravenous (IV) dosage form of PXD101 will confer a strategic advantage to our HDAC inhibitor development program," commented D. Frank Armstrong, President and CEO of CuraGen. "IV PXD101 may be preferable in mono or combination therapy against aggressive cancers, while the use of oral PXD101 may be preferable for maintenance or chronic treatment of relatively more indolent diseases such as bladder, prostate or thyroid cancers.
In a previously conducted pilot clinical study, oral PXD101 was demonstrated to achieve significant plasma concentrations and have an oral bioavailability of approximately 33 per cent These data, in part, support the continued evaluation of PXD101 in this comprehensive phase I trial.
CuraGen and TopoTarget continue to evaluate IV PXD101 in a number of Phase II trials including PXD101 monotherapy in patients with multiple myeloma (MM), T-cell lymphomas, and acute myelogenous leukaemia. In addition, multiple phase Ib/II clinical trials are being conducted to evaluate the combination of PXD101 with 5-fluorouracil for colorectal cancer, with carboplatin and paclitaxel for ovarian cancer, with cis-retinoic acid for advanced solid tumours, and with Velcade (bortezomib) for Injection for MM.