BMS-599626 in Treating Patients With Metastatic Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: BMS-599626 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase I trial is studying the side effects and best dose of BMS-599626 in treating patients with metastatic solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose, biologically active dose, and recommended phase II dose(s) of BMS-599626 in patients with metastatic HER2/neu-overexpressing primary solid tumors. Secondary Determine the safety and tolerability of this drug in these patients. Determine the pharmacokinetics of this drug in these patients. Determine the effect of this drug on biomarkers and predictive markers of HER1 and HER2 in skin and tumor in these patients. Evaluate tumor metabolic activity in response to this drug in these patients. Determine, preliminarily, evidence of anti-tumor activity of this drug in these patients. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients receive oral BMS-599626 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BMS-599626 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 20 patients are treated at that dose level. PROJECTED ACCRUAL: Approximately 3-60 patients will be accrued for this study within 1 year.

Official Title
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Phase I Study Of BMS-599626 In Patients With Advanced Solid Malignancies That Express Her2

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: BMS-59926


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed primary solid (i.e., non-hematologic) tumor Radiographic or tissue confirmation of metastatic disease Locally advanced disease allowed if no surgical or local therapeutic treatment exists HER2/neu overexpression (1+, 2+, or 3 +) by immunohistochemistry Tumors with HER2 gene amplification by fluorescence in situ hybridization analysis allowed Tumor paraffin tissue block OR 20-30 unstained slides from tumor tissue block must be available for biomarker and predictive marker analyses Disease progression during or after standard therapy OR no standard therapy exists Measurable or non-measurable disease Measurable disease is required for the expanded cohort treated at the maximum tolerated dose of the study drug No known brain metastasis Patients with controlled brain metastasis with no disease progression 60 days after prior therapy and no neurologic signs or symptoms are allowed Patients with signs or symptoms suggestive of brain metastasis are eligible provided that brain metastasis is ruled out by CT scan or MRI PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy At least 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT and AST ≤ 2.5 times ULN PT/PTT ≤ 1.5 times ULN INR ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 times ULN Calcium normal Cardiovascular LVEF ≥ 45% Heart rate ≥ 50 beats/min on electrocardiogram No uncontrolled cardiovascular disease No myocardial infarction within the past 12 months No uncontrolled angina within the past 6 months No congestive heart failure within the past 6 months No prolonged QTc (> 450 msec) on electrocardiogram No diagnosed or suspected congenital long QT syndrome No history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes) No history of second- or third-degree heart block Patients with pacemakers may be eligible No uncontrolled hypertension Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after study participation Potassium normal Magnesium normal No medical condition that has a risk of causing torsades de pointes No active infection No serious uncontrolled medical disorder that would preclude study participation No dementia or altered mental status that would preclude giving informed consent No known allergy to BMS-599626 or related compound No prisoners or patients involuntarily incarcerated for treatment of either a psychiatric or physical (e.g., infectious disease) illness PRIOR CONCURRENT THERAPY: Biologic therapy At least 4 weeks since prior immunotherapy At least 2 weeks since prior targeted kinase inhibitor (e.g., trastuzumab [Herceptin^®]) Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or doxorubicin HCl liposome) Endocrine therapy At least 2 weeks since prior anticancer hormonal therapy Radiotherapy At least 4 weeks since prior radiotherapy Surgery Not specified Other Recovered from prior therapy Prior adjuvant or neoadjuvant therapy allowed No short-acting antacids (e.g., Maalox^® or TUMS^®) 8 hours before or 4 hours after study drug administration No recent anticancer therapy More than 4 weeks since prior investigational agents At least 5 days (or 5 half-lives) since prior drugs that cause torsades de pointes At least 48 hours since prior proton pump inhibitors (e.g., omeprazole or lansoprazole) or histamine H_2 antagonists (e.g., ranitidine, famotidine, or cimetidine) Concurrent low-dose coumadin allowed No other concurrent investigational agents No concurrent drugs that may cause torsades de pointes or QTc prolongation

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: BMS-59926<br> | Drug: BMS-59926<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose of BMS-599626 |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific