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

Phase 1

Completed

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
RX-3117	RX-3117	All subjects will receive RX-3117.

Primary Outcome Measures

Name	Time	Method
Overall Safety Profile Characterized by # of Subjects With Dose-limiting Toxicities (DLTs) in Phase 1	28 days	Number of subjects participating in Phase 1 that experienced a DLT during the first cycle of treatment (28 days)
Overall Safety Profile Characterized by Number of Subjects Experiencing Serious Adverse Events in Phase 1	through study completion, up to 224 days (8 cycles of treatment)	Number of subjects participating in Phase 1 that experience any SAEs
Progression Free Survival (Phase 2)	4 months	Progression Free Survival in Phase 2 of the study for pancreatic and bladder cancer subjects.
Overall Safety Profile Characterized by the Number of Subjects That Discontinue Study Treatment - Phase 1	through study completion, up to 224 days (8 cycles of treatment)	Number of subjects participating in Phase 1 of study that discontinued study treatment due to a treatment emergent adverse event.
Overall Safety Profile Characterized by Number of Subjects Experiencing a Treatment Emergent Adverse Event- Phase 1	through study completion, up to 224 days (8 cycles of treatment)	Number of subjects that experience any treatment-related adverse event.

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration Time Curve (AUC) (Phase 1)	Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours after oral administration in Cycle 1 Days 1 and 15
Best Overall Response Rate (Phase 2)	Baseline and at 4, 8, 12, 16 and 32 weeks	Best Overall Response Rate (includes Complete Response, Partial Response, and Stable Disease)