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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 28, 2014