Know Cancer

forgot password

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

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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



- Determine the feasibility of neoadjuvant sunitinib malate in patients with newly
diagnosed, resectable stage II-IIIA breast cancer.


- 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

- 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

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.

Inclusion Criteria


- 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


- 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

- 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


- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including the

- Azole antifungals (ketoconazole, miconazole)

- Verapamil

- Clarithromycin

- HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,

- Erythromycin

- Delavirdine

- Diltiazem

- At least 12 days since prior and no concurrent CYP3A4 inducers, including the

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Maureen E. Trudeau, BSc, MA, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Edmond Odette Cancer Centre at Sunnybrook


Canada: Health Canada

Study ID:




Start Date:

March 2007

Completion Date:

January 2011

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms