Sunitinib in Treating Patients With Newly Diagnosed Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with newly diagnosed stage II or stage IIIA breast cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of neoadjuvant sunitinib malate in patients with newly diagnosed, resectable stage II-IIIA breast cancer. Secondary Determine the nature, severity, and frequency of adverse events in patients treated with this drug. Determine the response rate in patients treated with this drug. Evaluate markers of angiogenesis (e.g., VEGF receptor, platelet-derived growth factor receptor, circulating plasma VEGF, sVEGFR-2, sVEGFR-3, sKIT, and tumor vascularity) both pre- and post-treatment. Examine the role of both host- and tumor-specific genes pertaining to response and toxicity. Compare tumor vascular parameters pre- and post-treatment using DCE-MRI. Compare cell death and tumor microcirculation pre- and post-treatment using contrast-enhanced spectroscopic and microbubble contrast-enhanced ultrasound. Compare tumor metabolic activity pre- and post-treatment using fludeoxyglucose F 18-PET. OUTLINE: This is a multicenter study. Patients receive oral sunitinib malate once daily for 14-21 days in the absence of disease progression or unacceptable toxicity. Tissue samples are obtained by needle biopsy at baseline and once between days 14-21. Blood samples are collected at baseline, once between days 14-21, and at 4 weeks post-treatment for pharmacodynamic and other studies. Markers of angiogenesis (VEGF receptors, platelet-derived growth factor receptor, VEGF, sKIT, and tumor vascularity) are detected by immunohistochemistry. DCE-MRI and fludeoxyglucose F 18-PET are conducted for research studies at baseline and once between days 14-21. After completion of study treatment, patients are followed at 4 weeks.

Official Title
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A Feasibility Study of Pre-Operative Sunitinib (SU11248) With Multiple Pharmacodynamic Endpoints in Patients With T1c-T3 Operable Carcinoma of the Breast

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: sunitinib malate
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Procedure: needle biopsy
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Newly diagnosed disease Stage II-IIIA (T1c, T2, or T3) disease Unifocal disease Resectable disease Tumor must be suitable for multiple biopsies and imaging No prior breast cancer Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-1 Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine normal Calcium ≤ 3 mmol/L Bilirubin normal ALT and AST ≤ 2.5 times upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years No QTc prolongation (defined as a QTc interval ≥ 500 msec) or other significant ECG abnormalities No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) No prior or concurrent NYHA class II-IV cardiovascular disease No inadequately controlled hypertension (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) No myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months No pulmonary embolism within the past 12 months No cerebrovascular accident or transient ischemic attack within the past 12 months No serious illness or medical condition that would preclude study compliance including, but not limited to, the following: History of significant neurologic or psychiatric disorder Active uncontrolled infection Serious or nonhealing wound, ulcer, or bone fracture No medical condition that could interfere with oral medication intake (e.g., frequent vomiting, malabsorption) No history of allergic reactions attributed to compounds with similar chemical composition to sunitinib malate No preexisting hypothyroidism unless patient is euthyroid on medication PRIOR CONCURRENT THERAPY: At least 7 days since prior and no concurrent CYP3A4 inhibitors, including the following: Azole antifungals (ketoconazole, miconazole) Verapamil Clarithromycin HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir) Erythromycin Delavirdine Diltiazem At least 12 days since prior and no concurrent CYP3A4 inducers, including the following: Rifampin Phenytoin Rifabutin Hypericum perforatum (St. John's wort) Carbamazepine Efavirenz Pentobarbital Tipranavir Phenobarbital No prior protein tyrosine kinase inhibitor No prior antiangiogenic agent No prior hormonal therapy, radiotherapy, chemotherapy, surgery, investigational therapy, or other therapy for breast cancer At least 12 days since prior and no concurrent cyclooxygenase-2 inhibitors (e.g., etoricoxib, valdecoxib, celecoxib, dual cyclooxygenase/lipid oxidation, and lumiracoxib) No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide) No other concurrent treatment for breast cancer No concurrent coumadin-derivative anticoagulants (e.g., warfarin) Anticoagulants at ≤ 2 mg/day for prophylaxis of thrombosis allowed Low molecular weight heparin allowed provided INR ≤ 1.5

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: sunitinib malate|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacological study|nan|
|Procedure: needle biopsy|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nature, severity, and frequency of adverse events |  |  | 
| Activity (response rate) |  |  | 
| Markers of angiogenesis pre- and post-treatment |  |  | 
| Role of both host- and tumor-specific genes pertaining to response and toxicity |  |  | 
| Comparison of tumor vascular parameters pre- and post-treatment |  |  | 
| Comparison of cell death and tumor microcirculation pre- and post-treatment |  |  | 
| Comparison of tumor metabolic activity pre- and post-treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male breast cancer, stage II breast cancer, stage IIIA breast cancer