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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: sunitinib malate; Other: immunohistochemistry staining method; Other: flow cytometry

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sunitinib; 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	Other: laboratory biomarker analysis; Drug: sunitinib malate; Other: immunohistochemistry staining method; Other: flow cytometry

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): November 10, 2010
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: January 15, 2009
• First Submitted That Met QC Criteria: January 15, 2009
• First Posted (Estimate): January 16, 2009

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: March 9, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage II breast cancer; stage IIIC breast cancer; stage IA breast cancer; stage IB breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: 077539 (Other Identifier: University of California, San Francisco)