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

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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

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

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

- Clinically or radiologically evaluable disease

- No carcinomatous meningitis or untreated/uncontrolled metastatic brain parenchymal

- 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

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Mary Cianfrocca

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2001

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



Fox Chase Cancer Center Philadelphia, Pennsylvania  19111