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Phase I of Trastuzumab and Imatinib Mesylate (Gleevec®, Formerly Known as STI-571) in Patients With Recurrent or Metastatic Her-2/Neu Expressing Cancer


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I of Trastuzumab and Imatinib Mesylate (Gleevec®, Formerly Known as STI-571) in Patients With Recurrent or Metastatic Her-2/Neu Expressing Cancer


OBJECTIVES:

Primary

- Determine the maximum tolerated dose of imatinib mesylate when administered with
trastuzumab (Herceptin®) in patients with recurrent or metastatic
HER2/neu-overexpressing cancer.

- Determine response in patients treated with this regimen.

Secondary

- Correlate the number of circulating tumor cells with radiographic imaging in patients
treated with this regimen.

OUTLINE: This is a dose-escalation study of imatinib mesylate.

Patients receive trastuzumab (Herceptin®) IV over 90 minutes on day 1 and oral imatinib
mesylate once or twice daily on days 1-21. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 9-18 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed cancer that overexpresses HER2/neu,
measured 3+ by immunohistochemistry or positive by fluorescence in situ hybridization

- Recurrent or metastatic disease

- Meets 1 of the following criteria for measurable or evaluable disease:

- Unidimensionally measurable disease at least 20 mm by conventional techniques OR
at least 10 mm by spiral CT scan

- Evaluable disease, defined as a lesion on physical examination or imaging study
that can be assessed as to changes in size but cannot be clearly measured in 1
dimension (e.g., pleural effusions, ascites, or bone disease)

- No carcinomatous meningitis or untreated/uncontrolled metastatic brain parenchymal
disease

- Prior controlled brain parenchymal disease allowed provided at least 8 weeks
since prior therapy AND no symptomatic progression off corticosteroids

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- ALT and AST ≤ 2.0 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.0 times ULN

- Bilirubin ≤ 1.3 mg/dL

- No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis)

Renal

- Creatinine ≤ 2.0 mg/dL

Cardiovascular

- Ejection fraction ≥ lower limit of normal by MUGA

- No uncontrolled or significant cardiovascular disease

- No myocardial infarction within the past 6 months

- No ischemic heart disease requiring medication

- No congestive heart failure

Pulmonary

- No uncontrolled or significant pulmonary disease

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after study participation

- No active unresolved infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Prior trastuzumab (Herceptin®) allowed

- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) to support blood counts

- No other concurrent anticancer biologic agents

Chemotherapy

- Prior chemotherapy for metastatic disease allowed

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

- No concurrent anticancer chemotherapy

Endocrine therapy

- See Disease Characteristics

Radiotherapy

- At least 4 weeks since prior radiotherapy and recovered

Surgery

- More than 2 weeks since prior major surgery

Other

- At least 7 days since prior antibiotics

- No concurrent parenteral antibiotics

- No other concurrent anticancer agents

- No other concurrent investigational drugs

- No concurrent therapeutic anticoagulation with warfarin

- Concurrent mini-dose warfarin (1 mg/day) for prophylaxis of central venous
catheter thrombosis allowed

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of imatinib mesylate given concurrently with trastuzumab (Herceptin®) as measured by CTC v 3.0 at course 1

Safety Issue:

Yes

Principal Investigator

Margaret von Mehren, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000365451

NCT ID:

NCT00084513

Start Date:

August 2004

Completion Date:

March 2007

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

Name

Location

Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111