BMS-599626 in Treating Patients With Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00093730
Recruitment Status : Completed
First Posted : October 8, 2004
Last Update Posted : October 4, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

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
Unspecified Adult Solid Tumor, Protocol Specific Drug: BMS-59926 Phase 1

Detailed Description:



  • 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.


  • 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 : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study Of BMS-599626 In Patients With Advanced Solid Malignancies That Express Her2
Study Start Date : August 2004
Actual Primary Completion Date : April 2006

Arm Intervention/treatment
Experimental: BMS-59926 Drug: BMS-59926

Primary Outcome Measures :
  1. maximum tolerated dose of BMS-599626 [ Time Frame: 28 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • At least 3 months


  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL


  • 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


  • Creatinine ≤ 1.5 times ULN
  • Calcium normal


  • 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


  • 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


Biologic therapy

  • At least 4 weeks since prior immunotherapy
  • At least 2 weeks since prior targeted kinase inhibitor (e.g., trastuzumab [Herceptin^®])


  • 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


  • At least 4 weeks since prior radiotherapy


  • Not specified


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00093730

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Mark D. Pegram, MD Jonsson Comprehensive Cancer Center

Responsible Party: Jonsson Comprehensive Cancer Center Identifier: NCT00093730     History of Changes
Other Study ID Numbers: CDR0000389510
First Posted: October 8, 2004    Key Record Dates
Last Update Posted: October 4, 2012
Last Verified: October 2012

Keywords provided by Jonsson Comprehensive Cancer Center:
unspecified adult solid tumor, protocol specific