Effect of Vandetanib on Cellular Markers in Invasive Breast Cancer
Condition: Invasive Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Vandetanib; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: Female
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: breast cancer, TKI, tyrosine kinase inhibitor, vandetanib, Ki-67

Summary:

      The purpose of this project is to examine whether treatment with vandetanib has an effect on
      the tumor cells in breast cancer by examining tissue markers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with core breast biopsy that, on pathology review, demonstrates invasive
             breast cancer and are determined to need surgical excision of the lesion. All subtypes
             of invasive breast cancer will be enrolled. Core biopsy specimens of enrolled patients
             will be stained for RET by immunohistochemistry and scored, however, patients will not
             be excluded according to RET expression.

          -  Female gender

          -  Age >/= 18 years of age

          -  ECOG performance status </= 2

          -  Life expectancy of greater than 6 months

          -  Ability and willingness to provide informed consent to participate in study

        Exclusion Criteria:

          -  Prolonged QT interval (QTc > 480 milliseconds) on screening EKG or congenital long QT
             syndrome

          -  Any concomitant medications that are known to be associated with Torsades de Pointes
             or QT elongation (see appendix 2).

          -  Hypertension not controlled by medical therapy (systolic BP greater than 160
             millimeters of mercury [mmHg] or diastolic blood pressure great than 100 mmHg).

          -  Patients taking metformin or digoxin.

          -  History of arrhythmia (multifocal premature ventricular contractions, bigeminy,
             trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE
             Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or
             asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation
             controlled by medication are permitted.

          -  Significant cardiac event (e.g., myocardial infarction), superior vena cava syndrome,
             New York Heart Association (NYHA) classification of heart disease ≥2 within 12 weeks,
             or presence of cardiac disease that in the opinion of the Investigator increases the
             risk of ventricular arrhythmia.

          -  Serum calcium or magnesium outside the institutional range of normal.

          -  Serum Potassium < 4.0 mmol/L or above 5.0 mmol/L

          -  Creatinine clearance < 50 ml/min

          -  PT > 12 seconds or PTT > 31 seconds

          -  Platelet count of < 100,000

          -  Serum bilirubin greater than 1.5 mg/dl

          -  Alanine aminotransferase (ALT) > 50 U/L, aspartate aminotransferase (AST) > 65 U/L, or
             alkaline phosphatase (ALP) > 250 U/L

          -  Any cytotoxic treatments, such as neoadjuvant chemotherapy, planned before subsequent
             surgical procedure.

          -  Previous exposure to Vandetanib

          -  Previous enrollment or randomization in this study

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and staff at UIHC).

          -  Previous or current malignancies of other histologies within the last 5 years, with
             the exception of in situ carcinoma of the cervix, and adequately treated basal cell or
             squamous cell carcinoma of the skin.

          -  Patients who have received prior surgical site radiation.

          -  Patients on CYP3A4 inhibitors or inducers (see appendix 1).

          -  Inability to test core biopsy for study markers

          -  Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing must be
             performed within 2 weeks prior to randomization according to institutional standards
             for women of childbearing potential.)