A Study of ZD1839 Effects on Cell Proliferation in Breast Cancer

A Phase II, Randomised, Double-Blind, Placebocontrolled Study To Investigate The Effects Of ZD1839 (IRESSA™) On Cell Proliferation In Oestrogen And Progesterone Receptor Negative Breast Cancer Prior To Surgery

This is a Phase II, randomised, double-blind, placebo-controlled study. Subjects with histologically-confirmed oestrogen receptor negative (ER-), progesterone receptor negative (PgR-) primary breast cancer breast cancer will be randomly assigned in a 2:1 ratio to receive ZD1839 250 mg once daily or matching placebo for a total period of 5 weeks. Surgical intervention will take place after 4 weeks (on Day 29) and treatment will continue for 1 week after surgery.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Gefitinib

• Study Type: Interventional
• Enrollment: 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically-confirmed ER- and PgR- primary breast cancer
• Stage T .5 cm, N0-1, M0
• No previous treatment for breast cancer

Exclusion Criteria:

• ALT or AST greater than 2.5 times the ULRR
• Metastatic disease

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Estimate the effect of ZD1839 compared with placebo on the change in tumour cell proliferation in patients who have completely ER negative & PgR negative breast cancer
Aassessment of biomarker Ki-67 in breast cancer tissue at baseline by core biopsy and after 4 weeks on the surgical specimen

Secondary Outcome Measures

Outcome Measure
To assess the effect of 4 weeks of ZD1839 on the change in tumour size as assessed by ultrasounds.
To correlate the expression of tissue biomarkers (HER family and epidermal growth factor [EGF] related pathways) in the baseline biopsy sample and in the surgical (endpoint) specimen with the anti-proliferative effect of ZD1839.
To determine the effect of ZD1839 on HER-2 phosphorylation and other biomarkers in the surgical (endpoint) specimens when compared with the baseline biopsies
To assess the effect of ZD1839 on apoptosis as assessed by TUNEL in the surgical (endpoint) specimens when compared with the baseline biopsies
To determine plasma trough concentrations of ZD1839 and correlate these with molecular biomarkers detected in breast cancer tissue.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: AstraZeneca Italy Medical Director, MD, AstraZeneca; Principal Investigator: A Decensi, MD, Istituto Europeo di Oncologia di Milano

Study record dates

Study Major Dates

• Study Start: February 1, 2004

Study Registration Dates

• First Submitted: November 1, 2005
• First Submitted That Met QC Criteria: November 10, 2005
• First Posted (Estimate): November 15, 2005

Study Record Updates

• Last Update Posted (Estimate): January 28, 2011
• Last Update Submitted That Met QC Criteria: January 27, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: 1839IL/0509; D7913C00509 (Other Identifier: AZ IMPACT)