BMS-599626 in Treating Patients With Metastatic Solid Tumors

Jonsson Comprehensive Cancer Center

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: BMS-59926

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00093730

CDR0000389510

BMS-CA181002

UCLA-0404066-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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