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Anastrozole With or Without Gefitinib in Treating Postmenopausal Women With Metastatic or Locally Recurrent Breast Cancer

This study has been completed.
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC Identifier:
First received: August 6, 2003
Last updated: October 23, 2013
Last verified: October 2013

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by reducing the production of estrogen. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining anastrozole with gefitinib may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of anastrozole with or without gefitinib in treating postmenopausal women who have metastatic or locally recurrent breast cancer.

Condition Intervention Phase
Breast Cancer Drug: anastrozole Drug: gefitinib Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An EORTC Randomized, Double Blind, Placebo-Controlled, Phase II Multi-Center Trial Of Anastrozole (Arimidex) In Combination With ZD 1839 (Iressa) Or Placebo In Patients With Advanced Breast Cancer

Resource links provided by NLM:

Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival at 1 year [ Time Frame: at 1 year ]

Secondary Outcome Measures:
  • Tumor response as measured by RECIST [ Time Frame: from randomisation ]
  • Duration of response as measured by RECIST [ Time Frame: response duration ]
  • Safety as measured by CTC v2.0 [ Time Frame: from randomization ]

Enrollment: 71
Study Start Date: May 2003
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arimidex + Iressa® 250 mg
Arimidex + Iressa® 250 mg Treatment should be administered until documented disease progression, unacceptable toxicity as judged by the responsible physician or patient refusal
Drug: anastrozole Drug: gefitinib
Active Comparator: Arimidex + Placebo
Treatment should be administered until documented disease progression, unacceptable toxicity as judged by the responsible physician or patient refusal
Drug: anastrozole

Detailed Description:


  • Compare the 1 year antitumor activity of anastrozole with vs without gefitinib, in terms of progression-free survival, in postmenopausal women with metastatic or locally recurrent advanced breast cancer.
  • Compare the objective tumor response and duration of tumor response in patients treated with these regimens.
  • Compare the progression-free survival of patients treated with these regimens.
  • Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, dominant site of metastatic disease (bone alone vs other), prior chemotherapy (no vs yes), stage (metastatic vs locally recurrent), and measurability (measurable vs evaluable). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral anastrozole and oral gefitinib once daily.
  • Arm II: Patients receive oral anastrozole and an oral placebo once daily. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression.

PROJECTED ACCRUAL: A total of 108 patients (54 per treatment arm) will be accrued for this study.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically confirmed breast cancer

    • Radiologically or clinically evident metastatic or locally recurrent disease
    • Locally advanced disease in elderly patients
    • Bone metastases only allowed
  • Failed prior tamoxifen therapy
  • No rapidly progressive visceral metastases
  • No uncontrolled CNS metastases
  • Hormone receptor status:

    • Estrogen receptor and/or progesterone receptor positive



  • Postmenopausal


  • Female

Menopausal status

  • Postmenopausal, defined by any of the following:

    • Natural menopause with last menses more than 1 year ago
    • Radiotherapy-induced oophorectomy with last menses more than 1 year ago
    • Chemotherapy-induced menopause with last menses more than 1 year ago AND serum follicle-stimulating hormone and luteinizing hormone and plasma estradiol levels clearly in the postmenopausal range
    • Surgical castration

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Not specified


  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • Transaminases no greater than 2.5 times ULN
  • No unstable or uncompensated hepatic disease


  • No unstable or uncompensated renal disease


  • No unstable or uncompensated cardiac disease


  • No unstable or uncompensated pulmonary disease
  • No clinically active interstitial lung disease

    • Asymptomatic chronic stable radiographic changes are allowed


  • No severe or uncontrolled systemic disease
  • No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix, nonmelanoma skin cancer, or contralateral breast cancer
  • No psychological, familial, sociological or geographical condition that would preclude study compliance and follow-up
  • No grade 2 or greater unresolved chronic toxicity from prior anticancer therapy
  • No unresolved ocular inflammation or infection
  • No known hypersensitivity to anastrozole or gefitinib or any of their excipients


Biologic therapy

  • No prior trastuzumab (Herceptin)
  • No concurrent biologic therapy


  • No more than 1 line of prior chemotherapy in the adjuvant or metastatic setting
  • No concurrent chemotherapy

Endocrine therapy

  • At least 2 years since prior aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane) in the adjuvant setting
  • Prior tamoxifen or fulvestrant in the adjuvant and/or metastatic setting allowed
  • No prior aromatase inhibitors for metastatic disease
  • No other concurrent hormonal therapy


  • No concurrent radiotherapy to any metastatic site


  • No surgery during and within 4 days after the last dose of gefitinib


  • At least 30 days since prior investigational drugs
  • No prior anti-epidermal growth factor therapy
  • No prior anti-vascular endothelial growth factor therapy (i.e., tyrosine kinase inhibitor receptor)
  • No concurrent administration of any of the following drugs:

    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Phenobarbital
    • Hypericum perforatum (St John's Wort)
  • No other concurrent investigational drugs or treatment
  • No other concurrent cancer treatment
  • No concurrent systemic retinoids
  • Concurrent bisphosphonate therapy for the treatment and prevention of bony metastases is allowed provided therapy was initiated prior to study entry

    • Bisphosphonates may be initiated during study only for the treatment of hypercalcemia
  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 identifier: NCT00066378

Ziekenhuis Netwerk Antwerpen Middelheim
Antwerpen, Belgium, B-2020
Institut Jules Bordet
Brussels, Belgium, 1000
Algemeen Ziekenhuis Sint-Augustinus
Wilrijk, Belgium, 2610
Institut Bergonie
Bordeaux, France, 33076
Centre Henri Becquerel
Rouen, France, 76038
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066 CX
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Institute of Oncology - Ljubljana
Ljubljana, Slovenia, Sl-1000
United Kingdom
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Study Chair: Martine J. Piccart, MD, PhD Jules Bordet Institute
  More Information

Mauriac L, Cameron D, Dirix L: Results of randomized phase II trial combining Iressa (gefitinib) and arimidex in women with advanced breast cancer (ABC): EORTC protocol 10021. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-6133, 2008.

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00066378     History of Changes
Other Study ID Numbers: EORTC-10021
Study First Received: August 6, 2003
Last Updated: October 23, 2013

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on August 21, 2017