Breast Cancer
Conditions
Keywords
stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
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
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.
Interventions
DRUGsunitinib malate
OTHERflow cytometry
OTHERimmunohistochemistry staining method
OTHERlaboratory biomarker analysis
Sponsors
National Cancer Institute (NCI)
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Disseminated Tumor Cells (DTC) in Bone Marrow | Baseline, 6 months after start of treatment | DTCs were detected by immunomagnetic enrichment and flow cytometry (IE/FC) and measured in cells/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | up to 3 years from beginning of treatment | Data was not collected due to emerging data on toxicity and competing trials. |
| Effect of Sunitinib Malate on OTC in Peripheral Blood | After one year of treatment | Data was not collected due to emerging data on toxicity and competing trials. |
Participant flow
Recruitment details
Patients (pts) were enrolled in this study over the course of a year, from May 2009 through May 2010. A total of 21 patients were screened, and 13 patients, demonstrating ≥ 10 DTCs/mL via bone marrow aspiration, were deemed eligible.
Pre-assignment details
13 patients were enrolled, and 11 received 6-month bone marrow aspirations after completing sunitinib treatment.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib (SU) Eligible pts were treated with SU for 6 months (mo) at 37.5 mg/day. Concomitant hormonal therapy was allowed. Repeat BM aspirations were performed at 6 mo and one year. DTCs were detected by immunomagnetic enrichment + flow cytometry (IE/FC) | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Sunitinib (SU) |
|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 5 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
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
Time frame: Baseline, 6 months after start of treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sunitinib (SU) | Percent Change From Baseline in Disseminated Tumor Cells (DTC) in Bone Marrow | 39 percentage of change |
Secondary
Effect of Sunitinib Malate on OTC in Peripheral Blood
Data was not collected due to emerging data on toxicity and competing trials.
Time frame: After one year of treatment
Secondary
Number of Patients Who Are Able to Tolerate Sunitinib Malate for 6 Months and Complete the Study
Time frame: after 6 months from start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib (SU) | Number of Patients Who Are Able to Tolerate Sunitinib Malate for 6 Months and Complete the Study | 11 participants |
Secondary
Participants Affected by Toxicities as Assessed by NCI CTCAE v3.0
Time frame: up to 7 months after start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib (SU) | Participants Affected by Toxicities as Assessed by NCI CTCAE v3.0 | 13 participants |
Secondary
Relapse-free and Overall Survival
Data was not collected due to emerging data on toxicity and competing trials.
Time frame: up to 3 years from beginning of treatment