Dose-Finding and Safety Study for Oral Single-Agent to Treat Advanced Malignancies

A Phase 1, Open-Label, Dose-Ranging, Safety and Pharmacokinetic Study to Determine the Maximum Tolerated Dose of RX-3117 Administered Orally as a Single-Agent to Subjects With Advanced Malignancies

The purpose of this study is to determine the maximum tolerated dose of RX-3117 in subjects with advanced or metastatic solid tumors (Phase 1). The purpose of the Phase 2 portion is to estimate anti-tumor activity in subjects with advanced malignancies (relapsed or refractory pancreatic or advanced bladder cancer).

This is a dose-finding, open-label, single agent study of RX-3117. Once the maximum tolerated dose is identified additional subjects will be treated in a dose expansion followed by a 2-stage Phase 2 study. Subjects will be treated for up to 8 cycles of therapy. A cycle will be 4 weeks. RX-3117 dosing will be 3 times each week for 3 weeks follow by 1 week off treatment. All subjects will be followed for at least 30 days after the last dose of RX-3117.

Inclusion Criteria:

• Males or females who are 18 years or older
• Able to swallow capsules
• Histological or cytological evidence of confirmed metastatic pancreatic or advanced bladder cancer
• Able to discontinue all anticancer therapies 2 weeks prior to study start
• Measurable or evaluable disease using Response Evaluation Criteria in Solid Tumors
• Life expectancy of at least 3 months
• ECOG performance status of 0 or 1
• Provide written informed consent

Exclusion Criteria:

• Primary brain tumors or clinical evidence of active brain metastasis
• Systemic corticosteroid use within 7 days before planned start of study therapy
• Active infection requiring parenteral or oral antibiotics within 2 weeks before planned start of study therapy
• Uncontrolled diabetes as assessed by the investigator
• Prior or current history of hepatitis B, hepatitis C or human immunodeficiency virus
• History of bone marrow of solid organ transplantation
• History of congestive heart failure, arrhythmias, acute coronary syndrome or torsades de pointes
• Any other medical, psychiatric, or social condition, which in the opinion of the investigator, would preclude participation in the study, pose an undue medical hazard, interfere with the conduct of the study, or interfere with interpretation of the study results
• Known hypersensitivity to gemcitabine, azacytidine or cytosine arabinoside
• Pregnant, planning a pregnancy or breast feeding during the study
• Concurrent participation in another therapeutic clinical trial