CuraGen and TopoTarget Initiate Phase Ib Clinical Trial with PXD101 for Advanced Colorectal Cancer

Proof-of-Concept Trial Evaluating PXD101 Combination Therapy with 5- fluorouracil for Advanced Solid Tumors and Colorectal Cancer

29-Sep-2005

CuraGen Corporation and TopoTarget A/S announced the initiation of patient dosing in a Phase Ib open-label, multi-center, proof-of-concept clinical trial evaluating PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of advanced solid tumors, including colorectal cancer.

This proof-of-concept trial will initially enroll up to 15 patients with advanced solid tumors to establish the maximum tolerated dose (MTD) of PXD101 used in combination with 5-fluorouracil (5-FU), a drug widely used in the treatment of colorectal and other cancers. Following determination of the MTD, the study will be expanded and enroll up to 20 additional patients with advanced colorectal cancer in order to further evaluate the safety and activity of PXD101 combined with 5-FU in this patient population. In addition, the trial will assess the effect of PXD101 on thymidylate synthase (TS) expression in tumors. Patients will be enrolled at multiple sites in the United States, with preliminary results expected in the fourth quarter of 2006.

In preclinical in vitro studies, PXD101 demonstrated growth-inhibitory activity against a variety of tumor types, including colorectal cancer. PXD101 also showed activity against colorectal cancer in animal models and demonstrated activity that ranged from additive to synergistic when combined with 5-FU in animal and in vitro studies. Further preclinical studies have shown that PXD101 decreases TS expression, thereby providing a mechanistic basis for the observed synergy between PXD101 and 5-FU, as TS is an enzyme that is targeted by 5-FU. In addition, because elevated TS in colorectal cancer is correlated with resistance to 5-FU, decreasing TS levels with PXD101 has the potential to overcome TS-mediated 5-FU resistance in these tumors, thereby providing enhanced anti-cancer activity. These data support the evaluation of PXD101 used in combination with 5-FU in a clinical trial for the treatment of colorectal cancer and other solid tumors.

https://www.bionity.com/en/news/49235/curagen-and-topotarget-initiate-phase-ib-clinical-trial-with-pxd101-for-advanced-colorectal-cancer.html