746P - Phase I/II study of NC-6004, a novel micellar formulation of cisplatin, in combination with gemcitabine in patients with pancreatic cancer in Asia -...
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation II|
|Topics|| Drug Development
W. Su1, L. Chen2, C. Li3, J. Chen4, Y. Lin5, Y. Matsumura6, S. Choo7
NC-6004 is a cisplatin-incorporated polymeric micelle with a size of 30 nm in diameter composed of polyethylene glycol-polyglutamic acid block co-polymer via polymer-metal complex formation. A phase I study of NC-6004 monotherapy in patients with advanced solid tumours confirmed that NC-6004 exhibits delayed and sustained release of cisplatin characterized by lower Cmax and higher AUC compared to an equivalent dose of cisplatin, resulting in the reduction of cisplatin-related toxicity, and 2 out of 17 patients with pancreatic cancer demonstrated the evidence of disease stabilization. Preclinical studies demonstrated that NC-6004 in combination with gemcitabine (GEM) was effective against pancreatic cancer. On the basis of these results, phase I part of a phase I/II study of NC-6004 in combination with GEM in patients with pancreatic cancer has been conducted at 4 sites in Taiwan and 1 site in Singapore. The objectives of the study were to determine the MTD and RD of NC-6004 in combination with GEM in the treatment of pancreatic cancer for the following phase II study.Methods
A total of 19 patients with pancreatic cancer were treated with NC-6004 at a dose of 30, 60, 90 and 120 mg/m2 once every 3 weeks, and GEM at 1000 mg/m2 twice every 3 weeks on Day 1 and 8. The 2-dose oral steroid regimen was implemented to reduce the risk of hypersensitivity.Results
Two DLTs occurred at 120 mg/m2, which led to the conclusion that the MTD and the RD of NC-6004 in combination with GEM are 120 mg/m2 and approximately 90 mg/m2, respectively. In the interim analysis of ITT population for efficacy evaluation (17 patients), no patient had CR based on RECIST criteria, however best overall response (BOR) of PR was found in 1 (5.9%) and 10 (58.8%) had a BOR of SD, resulting in the disease control ratio of 64.7%. Because of the stringent prophylactic steroid regimen, eight out of 19 (42.1%) completed the per-protocol period (8 cycles; 24 weeks), and 1 of them reached cycles up to 20.Conclusion
Treatment with NC-6004 in combination with GEM was relatively well tolerated, and exhibited modest efficacy in patients with pancreatic cancer.Disclosure
All authors have declared no conflicts of interest.