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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00482755
First received: June 4, 2007
Last updated: June 20, 2013
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: sunitinib malate
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: needle biopsy
Procedure: neoadjuvant therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Feasibility Study of Pre-Operative Sunitinib (SU11248) With Multiple Pharmacodynamic Endpoints in Patients With T1c-T3 Operable Carcinoma of the Breast

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Feasibility [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Nature, severity, and frequency of adverse events [ Designated as safety issue: Yes ]
  • Activity (response rate) [ Designated as safety issue: No ]
  • Markers of angiogenesis pre- and post-treatment [ Designated as safety issue: No ]
  • Role of both host- and tumor-specific genes pertaining to response and toxicity [ Designated as safety issue: Yes ]
  • Comparison of tumor vascular parameters pre- and post-treatment [ Designated as safety issue: No ]
  • Comparison of cell death and tumor microcirculation pre- and post-treatment [ Designated as safety issue: No ]
  • Comparison of tumor metabolic activity pre- and post-treatment [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: March 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00482755

Locations
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Edmond Odette Cancer Centre at Sunnybrook
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Maureen E. Trudeau, BSc, MA, MD, FRCPC Edmond Odette Cancer Centre at Sunnybrook
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00482755     History of Changes
Other Study ID Numbers: MA29, CAN-NCIC-MA29, PFIZER-CAN-NCIC-MA29, CDR0000547161
Study First Received: June 4, 2007
Last Updated: June 20, 2013
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
male breast cancer
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014