Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer, stage IIIB breast cancer, inflammatory breast cancer, male breast cancer
Brief summary
RATIONALE: SU5416 may stop the growth of breast cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SU5416 with chemotherapy may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of combining SU5416 and doxorubicin in treating patients who have stage IIIB or stage IV inflammatory breast cancer.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer. * Determine the overall response, response rate, and progression-free survival rate of patients treated with this regimen. * Determine the antiangiogenic effects of this regimen in these patients. * Assess the relationship of plasma levels of these drugs with safety and efficacy in these patients. OUTLINE: This is a dose-escalation study. Patients receive doxorubicin IV continuously over 72 hours on days 1-3 of course 1. For all subsequent courses, patients receive doxorubicin as in course 1 and SU5416 IV over 1 hour twice weekly (on days 1 and 4) beginning on week 2 of course 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. After chemotherapy, all patients undergo a modified radical mastectomy and radiotherapy to the chest wall and regional lymph nodes. Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy. Cohorts of 3-6 patients receive escalating doses of SU5416 and doxorubicin 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. Once the MTD is determined, an additional 3 patients may be treated at that dose level. Patients are followed every 3 months until disease progression. PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 6-9 months.
Interventions
DRUGdoxorubicin hydrochloride
Patients receive doxorubicin IV continuously over 72 hours on days 1-3 of course 1. For all subsequent courses, patients receive doxorubicin as in course 1. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.
DRUGsemaxanib
For all subsequent courses, after course 1 patients SU5416 IV over 1 hour twice weekly (on days 1 and 4) beginning on week 2 of course 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.
PROCEDUREconventional surgery
Patients undergo a modified radical mastectomy.
RADIATIONradiation therapy
Patients undergo radiotherapy to the chest wall and regional lymph nodes.
DRUGtamoxifen
Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy.
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed stage IIIB or IV (supraclavicular lymph node involvement or metastasis) inflammatory breast cancer * Primary or secondary * No brain metastases or primary brain tumors * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age: * 18 and over Sex: * Male or female Menopausal status: * Not specified Performance status: * ECOG 0-2 Life expectancy: * At least 12 weeks Hematopoietic: * WBC at least 3,500/mm\^3 * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin greater than 9.0 g/dL Hepatic: * Bilirubin normal * AST and ALT less than 2 times upper limit of normal * PT and PTT normal OR * INR less than 1.1 Renal: * Creatinine less than 1.5 mg/dL OR * Creatinine clearance greater than 60 mL/min Cardiovascular: * LVEF at least 50% by MUGA * No New York Heart Association class III or IV heart disease * No uncompensated coronary artery disease * No myocardial infarction or unstable angina within the past 6 months * No deep venous or arterial thrombosis within the past 3 months Pulmonary: * No history of pulmonary embolism within the past 3 months Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No history of diabetes mellitus with severe peripheral vascular disease * No other prior or concurrent malignancies within the past 10 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix * No other uncontrolled illnesses PRIOR CONCURRENT THERAPY: Biologic therapy: * No concurrent epoetin alfa or filgrastim (G-CSF) Chemotherapy: * No more than 2 prior chemotherapy regimens allowed * No prior doxorubicin or other anthracycline Endocrine therapy: * Not specified Radiotherapy: * Prior radiotherapy allowed Surgery: * Not specified
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer. | Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. |
Countries
United States
Outcome results
None listed