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CuraGen and TopoTarget announce initiation of first NCI-sponsored clinical trial with PXD101

04-24-2006

CuraGen Corporation (CRGN) and TopoTarget A/S (TOPO) announced the initiation of patient dosing in a Phase I clinical trial evaluating the safety and tolerability of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in combination with bortezomib (Velcade) for the treatment of patients with advanced malignancies, including solid tumors and lymphomas.

This trial is being sponsored by the National Cancer Institute (NCI) under a Clinical Trials Agreement with CuraGen for PXD101 and under a Cooperative Research and Development Agreement (CRADA) with Millennium Pharmaceuticals Inc. for bortezomib. NCI-sponsored clinical trials with PXD101 are being conducted in parallel to those clinical trials sponsored by CuraGen, including the Phase Ib/II study of PXD101 plus Velcade (bortezomib) for the treatment of multiple myeloma initiated recently by CuraGen and TopoTarget.

This Phase I trial is an open-label, dose-escalation study being led by Dr. S. Gail Eckhardt, director of the Developmental Therapeutics and GI Malignancies Programs and professor of medicine at the University of Colorado Health Sciences Center. The study aims to establish the maximum tolerated dose (MTD) and safety profile of PXD101 in combination with bortezomib for patients with advanced solid tumors or lymphomas, which are refractory to standard therapies or for which no standard treatment exists.

Up to 36 patients will be enrolled in the dose escalation portion of the study and receive PXD101 and bortezomib in a three week cycle. Following determination of the MTD, the study will enroll approximately ten additional patients to further assess the biologic activity of PXD101 and bortezomib against tumor cells, including inhibition of HDAC and the proteasome.

"Based on the reported preclinical findings for PXD101 and bortezomib, these compounds appear to work through distinct pathways that are complementary to one another, and when combined, demonstrate synergistic activity against certain cancers in vitro. This Phase I study will build our knowledge and understanding of the safety and potential activity of the combination regimen, specifically for patients with refractory solid tumors or advanced lymphomas," stated Dr. Eckhardt, principal investigator.

In preclinical in vitro studies, PXD101 monotherapy demonstrated growth-inhibitory activity against a variety of solid tumor types. Furthermore, PXD101 monotherapy inhibited the growth of various hematological cancer cell lines, including lymphomas, at sub-micromolar potency and was highly active against cell lines that were resistant to other chemotherapeutics. Preclinical studies evaluating the combination of HDAC inhibitors and bortezomib have been reported in the literature and indicate synergistic anticancer activity against solid tumor and hematologic cancer cell lines.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.