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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: neoadjuvant therapy; Drug: sunitinib malate; Other: immunohistochemistry staining method; Procedure: needle biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Edmond Odette Cancer Centre at Sunnybrook

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Feasibility

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Maureen E. Trudeau, BSc, MA, MD, FRCPC, Toronto Sunnybrook Regional Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2009
• Primary Completion (Actual): March 15, 2010
• Study Completion (Actual): January 18, 2011

Study Registration Dates

• First Submitted: June 4, 2007
• First Submitted That Met QC Criteria: June 4, 2007
• First Posted (Estimated): June 5, 2007

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; male breast cancer; stage II 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: MA29; CAN-NCIC-MA29 (Other Identifier: PDQ Identifier); PFIZER-CAN-NCIC-MA29 (Other Identifier: Pfizer); CDR0000547161 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No