- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00093730
BMS-599626 in Treating Patients With Metastatic Solid Tumors
Phase I Study Of BMS-599626 In Patients With Advanced Solid Malignancies That Express Her2
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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095-1781
- Jonsson Comprehensive Cancer Center at UCLA
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BMS-59926
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
maximum tolerated dose of BMS-599626
Time Frame: 28 days
|
28 days
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- CDR0000389510
- UCLA-0404066-01
- BMS-CA181002
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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