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

Exclusion Criteria

• •Subjects who are homozygous for the UGT1A1\*28 allele
• •Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous IPs.
• •Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer.
• •Are currently receiving other medications intended for the treatment of their malignancy.
• •Women who are pregnant or breast feeding.
• •Taking a medication known to be clinically significant P-gp inhibitors or inducers within 14 days of treatment with Oratecan.
• •Chronically taking an oral medication known to be a P-gp substrate within 7 days of starting treatment with Oratecan.
• •Taking a medication known to be a clinically significant cytochrome (CYP) 3A4 strong inhibitor (eg, ketoconazole within 14 days) or strong inducers (eg, rifampin and St. John's Wort within 14 days) of starting treatment with Oratecan. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm
• •Require therapeutic use of anticoagulation medications
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements.
• •Major surgery to the upper gastrointestinal (GI) tract, or have a history of GI disease or other medical condition that, in the opinion of the investigator may interfere with oral drug absorption.
• •Allergy or sensitivity to irinotecan or cranberry-grape juice, or any of the irinotecan tablet excipients. .