CURAGEN, TOPOTARGET BEGIN NCI-SPONSORED OVARIAN CANCER TRIAL

CuraGen Cand TopoTarget have announced the initiation of patient dosing in a Phase II clinical trial evaluating the antitumor activity of intravenous PXD101, a small-molecule histone deacetylase (HDAC) inhibitor, for the treatment of ovarian cancer. The National Cancer Institute (NCI) is sponsoring this trial under a clinical trials agreement with CuraGen for PXD101.

The Phase II trial is an open-label study enrolling patients with either advanced platinum-resistant ovarian tumors or micropapillary/borderline low malignant potential (LMP) ovarian carcinoma. Patients may have received no more than three prior lines of therapy. Upon enrollment, patients will receive intravenous PXD101 daily for five days in three-week cycles until disease progression. The primary endpoint for the study is the determination of objective disease response, as evaluated by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints include evaluation of safety and tolerability of PXD101, stable disease rates, duration of response, progression-free survival, as well as median and overall survival. Up to 62 patients at sites in Canada and the United States will be enrolled into the study.

Correlative pharmacodynamic studies will also be conducted to evaluate the potential inhibition of HDACs in ovarian tumor cells from patients enrolled in this trial. Evaluation of the genes regulating proliferation and apoptosis (programmed cell death), as well as acetylation of histone and non-histone proteins, will be performed.

In an article published in the August issue of Molecular Cancer Therapeutics, CuraGen and TopoTarget scientists reported new preclinical data for PXD101 that is relevant to ovarian cancer. Data in the study demonstrates that PXD101 has growth-inhibitory activity as monotherapy or combination therapy on multidrug-resistant ovarian cancer lines, as well as on primary clinical cancer specimens grown in culture. Furthermore, PXD101 was found to have antitumor activity in animal models of ovarian cancer.