Phase Ii Open-Label, Safety, Pharmacolkinetic And Efficacy Study Of Panzem((R)) Ncd Administered Orally To Patients With Ovarian Cancer

A14 Background: 2-methoxyestradiol (2ME2; Panzem ® ) inhibits tumor cell proliferation and induces apoptosis by inhibiting microtubule polymerization and increasing reactive oxygen species-induced cell damage. In addition, 2ME2 downregulates HIF-1α at the posttranscriptional level and inhibits HIF-1α-mediated VEGF expression. Preclinical studies confirm that the agent has significant in vitro and in vivo activity in ovarian cancer xenograft models as monotherapy or in combination with paclitaxel. Based on these data, we performed a multi-center, phase 2 study to evaluate the efficacy and tolerability of Panzem ® Nanocrystal Colloidal Dispersion (NCD) in patients with recurrent epithelial ovarian cancer. Methods: Key eligibility criteria for the study included: presence of recurrent ovarian cancer, platinum resistant or refractory disease; presence of measurable or detectable disease by GCIC criteria; ECOG performance status 0 or 1; and adequate organ function. Panzem ® NCD was given orally 4 times per day at a dose of 1000mg (4gm/day). Patients were evaluated after every 28-day cycle. Efficacy endpoints included measurement of objective tumor response, measurement of detectable disease response, duration of progression free survival, assessment of relative change from baseline in CA-125 levels, and rate of overall clinical benefit. Results: Eighteen female patients were enrolled. The median age was 66 years (range, 40-73 years) and the median number of prior therapies was 4 (range 1-8). Forty-two cycles have been administered to date. Grade III-IV toxicities that occurred in more than one patient include fatigue (grade 4, n=2), dyspnea (grade 3, n=1; grade 4, n=1) and nausea (grade 3, n=3). Two patients died of progressive disease during the study or the immediate follow-up period. Five patients (27%) achieved stable disease lasting greater than 3 months. One patient had a 20% unconfirmed response by RECIST criteria. One patient had a confirmed partial response by CA-125 (251 U/mL at baseline to 110 U/mL) at Cycle 7. Follow-up is ongoing. Conclusions: Panzem ® NCD, administered as monotherapy daily, is well tolerated and associated with modest anti-tumor activity in patients with recurrent platinum resistant ovarian cancer. Further studies of Panzem ® NCD in combination with taxanes are planned.