A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer
18 Years
N/A
Both
Breast Cancer
Trial Information
A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer
OBJECTIVES:
Primary
- 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.
Secondary
- 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
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Male or female
Menopausal status
- Not specified
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Granulocyte count ≥ 1,500/mm^3
- Hemoglobin ≥ 8.0 g/dL
- Platelet count ≥ 100,000/mm^3
Hepatic
- 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)
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- No New York Heart Association class III or IV heart disease
- No congestive heart failure
- No myocardial infarction within the past 6 months
Other
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 14 days since prior systemic trastuzumab (Herceptin®)
- No concurrent trastuzumab
- No concurrent biologic therapy for the primary malignancy
Chemotherapy
- Prior taxane therapy, including docetaxel, in the adjuvant or metastatic setting
allowed
- 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
chemotherapy
- Concurrent megestrol allowed only as an appetite stimulant
Radiotherapy
- 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
Surgery
- See Disease Characteristics
- More than 2 weeks since prior major surgery
Other
- 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:
Interventional
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:
Yes
Principal Investigator
Antonio C. Wolff, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
J0214 CDR0000354504
NCT ID:
NCT00080665
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
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
