Phase 2 Anastrozole and Vandetanib (ZD6474) in Neoadjuvant Treatment of Postmenopausal Hormone Receptor-Positive Breast Cancer

NCT00481845 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB-08051BRSADJ000897923
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

In this study we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2 with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. The aim is to overcome mechanisms of resistance and simultaneously block multiple critical signaling pathways known to stimulate breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Tumor Objective Response by MRI

  Determine tumor objective response rate by MRI. (CR): Disappearance of the target lesion (PR): At least a 30% decrease in the longest diameter of the target lesion taking as reference the baseline LD (PD): At least a 20% increase in the LD of target lesion, taking as reference the baseline LD or the appearance of one or more new lesions (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the baseline LD.

  1 year

Secondary Outcomes (1)

• Pathologic Complete Response

  1 year

Study Arms (2)

Vandetanib + Anastrozole

EXPERIMENTAL

Vandetanib and Anastrozole as neoadjuvant therapy

Drug: Vandetanib; Drug: Anastrozole

Anastrozole

ACTIVE COMPARATOR

Anastrozole as neoadjuvant therapy

Drug: Anastrozole

Interventions

Vandetanib DRUG

300 mg daily

Also known as: Zactima, ZD6474

Vandetanib + Anastrozole

Anastrozole DRUG

1 mg daily

Also known as: Arimidex

Anastrozole; Vandetanib + Anastrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed invasive, hormone receptor-positive (ER and/or PR positive) breast cancer
• Stage I-III breast cancer including any primary tumor ≥ 1 cm by ultrasound
• Diagnosis by core needle biopsy with placement of metallic clip at tumor site
• Sentinel lymph node biopsy (US-guided FNA may be substituted if palpable axillary lymphadenopathy)
• Evaluation by a surgeon to determine eligibility for breast conservation
• Postmenopausal status (age ≥ 60 yo; or \< 60 yo and FSH and estradiol in the postmenopausal range, prior bilateral oophorectomy)
• Serum creatinine \< 1.5 x upper limit of normal (ULN) or creatinine clearance \> 50 mL/minute (calculated by Cockcroft-Gault formula.)
• Serum bilirubin \< 1.5 x ULN
• Serum potassium ≥ 4 mmol/L (supplementation allowed)
• Serum calcium or magnesium within normal range (supplementation allowed)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 x ULN or alkaline phosphatase (ALP) ≤ 2.5 x ULN
• ECOG Performance Status 0,1,2
• ECG QTc \< 480 msec
• Measurable disease
• Written, informed consent

You may not qualify if:

• Metastatic breast cancer excluding disease in regional lymph nodes
• Inoperable disease considered irreversible with neoadjuvant endocrine therapy
• HER2-overexpressed breast cancer
• Prior chemotherapy or radiotherapy for the treatment of the current breast cancer
• Prior hormonal therapy for the treatment of the current breast cancer
• Prior surgical biopsy, lumpectomy, mastectomy for the current breast cancer
• Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol
• Currently active diarrhea that may affect the ability of the patient to absorb ZD6474 or tolerate diarrhea
• Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease \>2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia (VT) or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained VT. Atrial fibrillation controlled on medication is not excluded.
• Previous history of QTc prolongation as a result of another medication that required discontinuation of that medication.
• Congenital long QT syndrome or 1st degree relative with unexplained sudden death \< 40 years of age.
• Presence of left bundle branch block (LBBB).
• QTc with Bazett's correction that is unmeasurable, or ≥ 480 msec on screening ECG. If a patient has QTc ≥ 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be \< 480 msec in order for the patient to be eligible for the study.
• Use of any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function.

Sponsors & Collaborators

• Stanford University: lead
• AstraZeneca: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

vandetanib; Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mark Daniel Pegram; Susy Yuan-Huey Hung Professor
• Organization: Stanford Cancer Institute, Stanford University

mpegram@stanford.edu

650-723-5801

Study Officials

• Mark D Pegram, MD

  Stanford Cancer Institute, Stanford University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Susy Yuan-Huey Hung Professor

Study Record Dates

• First Submitted: May 31, 2007
• First Posted: June 4, 2007
• Study Start: January 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: February 7, 2017
• Results First Posted: February 7, 2017

Record last verified: 2016-12

Locations

US (1)