BMS-214662 Plus Trastuzumab in Treating Patients With Advanced 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: NCT00022529
Recruitment Status : Completed
First Posted : June 17, 2003
Last Update Posted : January 25, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Phase I trial to study the effectiveness of BMS-214662 plus trastuzumab in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: BMS-214662 Biological: trastuzumab Other: pharmacological study Phase 1

Detailed Description:


I. Determine the maximum tolerated dose and recommended phase II dose of BMS-214662 when combined with trastuzumab (Herceptin) in patients with advanced solid tumors.

II. Determine the dose-limiting toxic effects of this regimen in these patients.


I. Determine the pharmacokinetics of this regimen in these patients. Ii. Determine, in a preliminary manner, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of BMS-214662.

Patients receive BMS-214662 IV over 1 hour on days 2, 8, 15, and 22 and trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BMS-214662 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, additional patients are accrued to receive treatment with BMS-214662 and trastuzumab at the recommended phase II dose.

PROJECTED ACCRUAL: A total of 3-28 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Intravenous BMS-214662 FTI (NSC# 710086) and Herceptin (NSC# 688097) Weekly in Patients With Advanced Malignancies
Study Start Date : July 2001
Actual Primary Completion Date : January 2004

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Treatment (BMS-214662, trastuzumab)
Patients receive BMS-214662 IV over 1 hour on days 2, 8, 15, and 22 and trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: BMS-214662
Given IV
Other Names:
  • farnesyltransferase inhibitor BMS-214662
  • FTI BMS 214662

Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Primary Outcome Measures :
  1. MTD defined as the highest dose level at which =< 1/6 subjects experience a study related dose-limiting toxicity (DLT) as assessed by CTC version 2.0 [ Time Frame: 28 days ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically or cytologically confirmed solid tumor that is unresponsive to currently available therapies or for which no known effective therapy exists
  • Overexpressing HER-2-neu (2+ or 3+) by immunohistochemistry or fluorescent in situ hybridization
  • Clinically or radiologically evaluable disease
  • No carcinomatous meningitis or untreated/uncontrolled metastatic brain parenchymal disease

    • At least 8 weeks since prior therapy for prior brain parenchymal disease and asymptomatic off corticosteroids
  • Performance status - ECOG 0-2
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.8 mg/dL
  • ALT and AST no greater than 1.5 times upper limit of normal (ULN)
  • Creatinine no greater than 1.5 times ULN
  • No uncontrolled or significant cardiovascular disease
  • No myocardial infarction within the past 6 months
  • No prior clinically significant atrial or ventricular arrhythmias
  • No prior second or third degree heart block
  • No ischemic heart disease requiring medication
  • No congestive heart failure
  • Corrected QT interval no greater than 450 milliseconds by electrocardiogram
  • Ejection fraction at least lower limit of normal by MUGA scan
  • No uncontrolled or significant pulmonary disease
  • No active unresolved infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study
  • At least 4 weeks since prior immunotherapy, including trastuzumab (Herceptin), and recovered
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No anthracyclines for at least 22 weeks after completion of study therapy
  • No other concurrent chemotherapy
  • Concurrent hormone replacement therapy allowed
  • No other concurrent hormonal therapy
  • At least 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy to more than 25% of the bone marrow-containing skeleton
  • No concurrent radiotherapy
  • At least 4 weeks since prior investigational agents and recovered
  • At least 7 days since prior known substrates of cytochrome P450-3A4 (CYP3A4)
  • At least 7 days since prior parenteral antibiotics
  • No concurrent substrates of CYP3A4
  • No concurrent parenteral antibiotics
  • No other concurrent experimental medications

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): NCT00022529

United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Mary Cianfrocca Fox Chase Cancer Center

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00022529     History of Changes
Other Study ID Numbers: NCI-2012-02396
CDR0000068828 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: June 17, 2003    Key Record Dates
Last Update Posted: January 25, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Antineoplastic Agents