SU5416 and Doxorubicin in Treating Patients With Stage IIIB or Stage IV Inflammatory Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I Pharmacokinetic, Pharmacodynamic, and Clinical Study of the Combination of the Angiogenesis Inhibitor SU5416 and Doxorubicin in Inflammatory Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: doxorubicin hydrochloride
* Drug: semaxanib
* Procedure: conventional surgery
* Radiation: radiation therapy
* Drug: tamoxifen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: doxorubicin 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.|
|Drug: semaxanib|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.|
|Procedure: conventional surgery|Patients undergo a modified radical mastectomy.|
|Radiation: radiation therapy|Patients undergo radiotherapy to the chest wall and regional lymph nodes.|
|Drug: tamoxifen|Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer, stage IIIB breast cancer, inflammatory breast cancer, male breast cancer