Effect of Vandetanib on Cellular Markers in Invasive Breast Cancer

A Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Effect of Vandetanib on Cellular Markers of Proliferation and Apoptosis in Invasive Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Invasive Breast Cancer
• Intervention / Treatment: Other: Placebo; Drug: Vandetanib

Detailed Description

The purpose of this research study is to test whether vandetanib has an effect on tumor growth markers. Vandetanib is not approved by the FDA for use in treating breast cancer. This study will compare vandetanib to a placebo.

The proposed study is designed to determine the change in Ki-67 expression on paired breast cancer samples obtained before and after treatment with vandetanib. Other tumor markers including RET, TUNEL and phosphorylation specific levels of ERK1/2, AKT and mTOR will also be assessed on the paired samples.

Those who have a core biopsy of the breast which demonstrates invasive breast cancer and requires surgical excision of the lesion will be eligible for inclusion in the study. The tyrosine kinase inhibitor, vandetanib 300 mg, will be given once a day for 7-14 days prior to surgery. Following surgery, tissue markers would be analyzed on each of the paired samples, allowing for rapid assessment of in vivo response to TKI treatment.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vandetanib; Vandetanib, 300 mg, PO, q day for 7-14 days prior to surgery	Drug: Vandetanib; Other Names: ZD6474
Placebo Comparator: Placebo; Placebo, PO, q day for 7-14 days prior to surgery.	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Ki-67 Cells Observed 2 Weeks Post-treatment	Pre- and post-treatment samples will be assessed by immunohistochemistry for positivity for Ki-67.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in TUNEL Observed 2 Weeks Post-treatment	Pre- and post-treatment samples will be assessed by immunohistochemistry for positivity for TUNEL.	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in RET Expression Observed 2 Weeks Post-treatment	Results will be stratified by RET gene expression, a negative prognostic indicator in breast cancer, to demonstrate that RET is a marker of response.	2 weeks

Collaborators and Investigators

• Sponsor: Ronald Weigel
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Ronal Weigel, MD, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): December 21, 2018
• Study Completion (Actual): December 21, 2018

Study Registration Dates

• First Submitted: August 29, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimate): September 4, 2013

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer, TKI, tyrosine kinase inhibitor, vandetanib, Ki-67
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 201301763

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