Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief summary
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
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.
Interventions
Sponsors
Study design
Eligibility
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| maximum tolerated dose of BMS-599626 | 28 days |
Countries
United States