BMS-599626 in Treating Patients With Metastatic Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BMS-59926
|
Drug: BMS-59926
|
Outcome Measures
Primary Outcome Measures
- maximum tolerated dose of BMS-599626 [28 days]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically or cytologically confirmed primary solid (i.e., non-hematologic) tumor
-
Radiographic or tissue confirmation of metastatic disease
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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
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Tumor paraffin tissue block OR 20-30 unstained slides from tumor tissue block must be available for biomarker and predictive marker analyses
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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
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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
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Patients with pacemakers may be eligible
-
No uncontrolled hypertension
Other
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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
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More than 4 weeks since prior investigational agents
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At least 5 days (or 5 half-lives) since prior drugs that cause torsades de pointes
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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)
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Concurrent low-dose coumadin allowed
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No other concurrent investigational agents
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No concurrent drugs that may cause torsades de pointes or QTc prolongation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jonsson Comprehensive Cancer Center at UCLA | Los Angeles | California | United States | 90095-1781 |
Sponsors and Collaborators
- Jonsson Comprehensive Cancer Center
- National Cancer Institute (NCI)
Investigators
- Study Chair: Mark D. Pegram, MD, Jonsson Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000389510
- UCLA-0404066-01
- BMS-CA181002