Sunitinib in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer Who Have Tumor Cells in the Bone Marrow

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. PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with stage I, stage II, or stage III breast cancer who have tumor cells in the bone marrow.

Detailed Description
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OBJECTIVES: Primary To determine the effect of sunitinib malate on occult tumor cells (OTC) in the bone marrow of patients with high-risk stage I-III breast cancer. Secondary To evaluate the number of patients who are able to tolerate this drug for 6 months and complete the study. To evaluate the toxicities of this drug in these patients. To evaluate the effects of this drug on OTC in peripheral blood. To evaluate correlative markers, including endothelial cells, soluble cKIT, and VEGF. To evaluate relapse-free and overall survival of patients treated with this drug. OUTLINE: Patients receive oral sunitinib malate once daily for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and peripheral blood sample collection at baseline and at 6 and 12 months. Bone marrow aspirate samples are analyzed by IHC and flow cytometry. Peripheral blood samples are analyzed for circulating tumor cells. After completion of study treatment, patients are followed at 1 and 6 months.

Official Title
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Pilot Study to Evaluate the Effect of Sunitinib on Occult Tumor Cells in the Bone Marrow of Patients With High Risk Early Stage Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: sunitinib malate
* Other: flow cytometry
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed high-risk breast cancer Stage I-III disease Has undergone definitive surgery with or without radiotherapy Completely resected disease Bone marrow aspirate positive for occult tumor cells, defined as ≥ 10 occult tumor cells/mL by IHC and flow cytometry If the patient received either no adjuvant therapy or hormonal therapy alone, the aspiration may have been performed at diagnosis as part of the large micrometastasis study at UCSF, or following diagnosis if the patient underwent initial surgery elsewhere (or underwent surgery following neoadjuvant therapy for breast cancer) If the patient received adjuvant chemotherapy, the aspiration must have been performed ≥ 3 weeks after completion of chemotherapy Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified ECOG performance status 0-1 WBC count normal (3.4-10 x 10^9/L) Hemoglobin > 9.0 g/dL Platelet count normal (140-450 x 10^9/L) ANC normal (1.8-6.8 x 10^9/L) Serum creatinine ≤ 1.5 times upper limit of normal (ULN) Total bilirubin ≤ 1.5 times ULN Alkaline phosphatase ≤ 1.5 times ULN AST and ALT ≤ 2.5 times ULN TSH and T4 levels normal LVEF > 50% Systolic BP < 140 mm Hg and diastolic BP < 90 mm Hg Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of HIV infection No concurrent severe illness that would likely preclude study compliance No other malignancy within the past 5 years except basal cell carcinoma of the skin PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior sunitinib malate Prior adjuvant chemotherapy, including trastuzumab (Herceptin®), allowed provided it was completed within the past 6 months Prior surgery following neoadjuvant chemotherapy or hormonal therapy allowed No concurrent potent CYP3A4 inducers No concurrent trastuzumab Concurrent hormonal therapy or radiotherapy allowed

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sunitinib<br>Study to evaluate the effect of sunitinib (37.5 mg/day orally for 6 months) on occult tumor cells in the bone marrow of patients with high risk early stage breast cancer | Drug: sunitinib malate<br> <br> Other: flow cytometry<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Disseminated Tumor Cells (DTC) in Bone Marrow | DTCs were detected by immunomagnetic enrichment and flow cytometry (IE/FC) and measured in cells/mL | Baseline, 6 months after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Are Able to Tolerate Sunitinib Malate for 6 Months and Complete the Study |  | after 6 months from start of treatment | 
| Participants Affected by Toxicities as Assessed by NCI CTCAE v3.0 |  | up to 7 months after start of treatment | 
| Relapse-free and Overall Survival | Data was not collected due to emerging data on toxicity and competing trials. | up to 3 years from beginning of treatment | 
| Effect of Sunitinib Malate on OTC in Peripheral Blood | Data was not collected due to emerging data on toxicity and competing trials. | After one year of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer