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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumor, Metastatic Bladder Cancer

Intervention / Treatment
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* Drug: RX-3117


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RX-3117<br>All subjects will receive RX-3117. | Drug: RX-3117<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Best Overall Response Rate (includes Complete Response, Partial Response, and Stable Disease) | Baseline and at 4, 8, 12, 16 and 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oncology, tumor, metastatic, bladder