A Dose-regimen Finding Study to Evaluate Safety, Tolerability, Pharmacokinetics and Activity of Oratecan in Subjects With Advanced Malignancies

This study consists of Part 1 and Part 2. Part 1 of this study is a "3+3" design to define the MTD of Oratecan in up to 60 evaluable subjects. It will be conducted in 2 parts; 1A will test the oral liquid formulation and 1B will test the oral tablet formulation of irinotecan. Part 2 will enroll an additional 10 subjects at the Part 1 MTD to further characterize the safety, tolerability, pharmacokinetics, and activity of Oratecan at that dose. Irinotecan (CPT-11) is a potent anticancer drug under the class of camptothecins that is marketed under the trade name Camptosar. Irinotecan is a prodrug that is activated via carboxylesterase in liver and intestines to its active form, SN38 which is approximately 1000 times more cytotoxic than irinotecan itself. The investigational product (IP) Oratecan is comprised of the approved drug irinotecan with HM30181 methanesulfonate monohydrate (HM30181), a novel p-glycoprotein (P-gp) pump inhibitor. Oratecan is intended for the treatment of irinotecan-responsive cancers. The antitumor activity of Oratecan is due to the action of irinotecan. Combining HM30181 with irinotecan allows intestinal absorption and systemic exposure of irinotecan and its active metabolite, SN38, at therapeutic levels after oral administration.