BMS-599626 in Treating Patients With Metastatic Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00093730
First received: October 6, 2004
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Of BMS-599626 In Patients With Advanced Solid Malignancies That Express Her2

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose of BMS-599626 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: August 2004
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMS-59926 Drug: BMS-59926

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00093730

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Study Chair: Mark D. Pegram, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00093730     History of Changes
Other Study ID Numbers: CDR0000389510, UCLA-0404066-01, BMS-CA181002
Study First Received: October 6, 2004
Last Updated: October 3, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 14, 2014