Ascending Multiple-Dose Study of BMS-817378 in Subjects With Advanced Cancers

Study Overview
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Brief Summary
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The purpose of this study is to find the maximum tolerated dose of BMS-817378 in subjects with advanced cancers

Official Title
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A Phase I Ascending Multiple-Dose Study of BMS-817378 in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: BMS-817378


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of advanced non-hematologic malignancy. Dose expansion cohort restricted to subjects with advanced or metastatic gastroesophageal cancer, squamous cell cancers of the head and neck, and castration resistant prostate cancer ECOG status 0-1 Exclusion Criteria: WOCBP unwilling/unable to use acceptable contraception methods, and women pregnant or breast feeding Symptomatic brain metastasis Uncontrolled or significant cardiovascular disease History of thromboembolic events or bleeding diathesis in past 6 months Conditions requiring prophylactic anticoagulation or chronic anti-platelet therapy Serious non-healing wounds, ulcers or bone fractures in past 3 months Hemorrhage or bleeding event >= CTCAE grade 3 in past 4 weeks Proteinuria >= 2+ on dipstick or >= 1gm/24 hours Concurrent chemotherapy, hormonal therapy, immunotherapy, radiation therapy or therapy with any other investigational product Concurrent herbal, alternative, food supplements, or strong CYP 3A4 inhibitors or inducers

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: Single Arm<br> | Drug: BMS-817378<br>* Capsule, Oral, Dose escalation to a MTD from a starting dose of 25 mg, once daily, until disease progression/subject discontinuation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the MTD of BMS-817378 when administered orally on a daily schedule in subjects with advanced cancers |  | Within the first 21 days after first dose of BMS-817378 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess safety and tolerability of multiple doses of BMS-817378 administered orally on a once daily schedule in subjects with advanced or metastatic solid tumors |  | All time points while subject is on study | 
| Assess the safety and tolerability of co-administration of a CYP substrate cocktail and BMS-817378 given at or below the MTD (dose expansion cohort) |  | Day 22 +/-2 | 
| Characterize the pharmacokinetics of BMS-817378 and its active moiety, BMS-794833 |  | Days 1 and 15 | 
| Assess the effects of BMS-817378 and BMS-794833 on blood pressure, heart rate, ECG intervals, and left ventricular ejection fraction |  | All time points while subject is on study | 
| Describe preliminary evidence for anti-tumor activity of BMS-817378 |  | Every 6 weeks |