BMS-214662 Plus Trastuzumab in Treating Patients With Advanced Solid Tumors

January 24, 2013 updated by: National Cancer Institute (NCI)

Phase I Study of Intravenous BMS-214662 FTI (NSC# 710086) and Herceptin (NSC# 688097) Weekly in Patients With Advanced Malignancies

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Biological: trastuzumab
Given IV
Other Names:
  • Herceptin
  • anti-c-erB-2
  • MOAB HER2
Drug: BMS-214662
Given IV
Other Names:
  • farnesyltransferase inhibitor BMS-214662
  • FTI BMS 214662

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Mary Cianfrocca, Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2001

Primary Completion (Actual)

January 1, 2004

Study Registration Dates

First Submitted

August 10, 2001

First Submitted That Met QC Criteria

June 16, 2003

First Posted (Estimate)

June 17, 2003

Study Record Updates

Last Update Posted (Estimate)

January 25, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02396
  • FCCC-01013
  • CDR0000068828 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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