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A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer

Phase 1
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer



- Determine the safety profile, maximum tolerated dose, and recommended phase II dose of
docetaxel when administered with imatinib mesylate in patients with locally advanced or
metastatic breast cancer.


- Determine the pharmacokinetic profile of this regimen in these patients.

- Determine the potential effects of this regimen on CYP3A4 activity and docetaxel
metabolism in these patients.

- Correlate docetaxel and imatinib mesylate exposure (utilizing total and unbound
docetaxel and imatinib mesylate plasma concentrations) with drug response (e.g.,
pharmacodynamic effects, drug toxicity, and response) in these patients.

- Determine response rate, duration of response, and time to treatment failure in
patients treated with this regimen.

- Correlate proteomic profile changes in serum with tumor burden and response in patients
treated with this regimen.

- Correlate pharmacokinetic parameters, tissue expression of specific receptor tyrosine
kinases (e.g., c-Kit, platelet-derived growth factor receptor [PDGFR], and
phosphorylated PDGFR) in paraffin blocks, and pharmacodynamic assays with antitumor
activity of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of docetaxel.

Patients receive docetaxel IV over 1 hour on days 1, 8, and 15 and oral imatinib mesylate
(STI571) on days 8-28 of course 1 and days 1-28 of all subsequent courses. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity*. Patients with
stable or responding disease after at least 2 courses of therapy may discontinue docetaxel
and continue therapy with single-agent STI571 until disease progression.

NOTE: *Patients experiencing excessive docetaxel-related toxicity who have completed at
least 2 full courses may continue on single-agent STI571 in the absence of disease
progression or excessive STI571-related toxicity.

Cohorts of 3-6 patients receive escalating doses of docetaxel 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. An additional cohort of 6-12 patients
receives treatment at the MTD.

Patients are followed at 30 days.

PROJECTED ACCRUAL: Approximately of 18-30 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed adenocarcinoma of the breast

- Stage IIIB, IIIC, or IV disease

- Measurable or evaluable disease

- Stable brain metastases allowed provided prior surgery or radiotherapy was completed
more than 90 days ago

- No documented or suspected leptomeningeal disease

- Hormone receptor status:

- Not specified



- 18 and over


- Male or female

Menopausal status

- Not specified

Performance status

- ECOG 0-1

Life expectancy

- Not specified


- Granulocyte count ≥ 1,500/mm^3

- Hemoglobin ≥ 8.0 g/dL

- Platelet count ≥ 100,000/mm^3


- Bilirubin ≤ upper limit of normal (ULN)

- Meets 1 of the following criteria for AST or ALT AND alkaline phosphatase:

- AST or ALT ≤ ULN AND alkaline phosphatase ≤ 5 times ULN

- AST or ALT ≤ 2.5 times ULN AND alkaline phosphatase ≤ ULN

- AST or ALT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN

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


- Creatinine ≤ 1.5 mg/dL


- No New York Heart Association class III or IV heart disease

- No congestive heart failure

- No myocardial infarction within the past 6 months


- Not pregnant or nursing

- Negative pregnancy test

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

- No other primary malignancy except those malignancies that are clinically
insignificant AND do not require active intervention

- No other concurrent severe and/or life-threatening medical disease

- No significant history of noncompliance to medical regimens or inability to grant
reliable informed consent


Biologic therapy

- At least 14 days since prior systemic trastuzumab (Herceptin®)

- No concurrent trastuzumab

- No concurrent biologic therapy for the primary malignancy


- Prior taxane therapy, including docetaxel, in the adjuvant or metastatic setting

- At least 21 days since prior systemic chemotherapy (14 days for weekly or oral
chemotherapy and 42 days for nitrosoureas or mitomycin)

- No other concurrent chemotherapy

Endocrine therapy

- At least 14 days since prior systemic hormonal therapy

- No concurrent antiestrogen therapy

- No concurrent routine systemic corticosteroid therapy except as premedication for

- Concurrent megestrol allowed only as an appetite stimulant


- See Disease Characteristics

- At least 14 days since prior radiotherapy

- No prior radiotherapy to only site of measurable/evaluable disease unless there is
new evidence of post-radiotherapy disease progression

- No concurrent radiotherapy


- See Disease Characteristics

- More than 2 weeks since prior major surgery


- Recovered from all prior therapy

- At least 14 days since prior daily or weekly systemic investigational treatment

- No concurrent warfarin for full anticoagulation

- Concurrent low-dose warfarin (e.g., 1 mg/day) allowed for prophylaxis of central
venous access

- No concurrent treatment with any of the following:

- Phenobarbital

- Phenytoin

- Carbamazepine

- Barbiturates

- Rifampin

- Hypericum perforatum (St. John's wort)

- No other concurrent therapies for the primary malignancy

- No other concurrent investigational drugs or systemic therapy

- No concurrent bisphosphonates unless started before study therapy

- No concurrent grapefruit juice

Type of Study:


Study Design:

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

Outcome Measure:

2.1.1 To determine the safety profile, maximum tolerated dose, and recommended dose for subsequent phase II studies of a combination regimen of daily STI571 with weekly docetaxel on days 1, 8, and 15 in a 28-day cycle.

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Antonio C. Wolff, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Federal Government

Study ID:

J0214 CDR0000354504



Start Date:

December 2003

Completion Date:

January 2011

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410