Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Postmenopausal	Other	EORTC-10021 IDBBC-10021, NCT00066378

Objectives

1. 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.
2. Compare the objective tumor response and duration of tumor response in patients treated with these regimens.
3. Compare the progression-free survival of patients treated with these regimens.
4. Compare the safety of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

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

Chemotherapy

• 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

Radiotherapy

• No concurrent radiotherapy to any metastatic site

Surgery

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

Other

• 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

Patient Characteristics:

Age

• Postmenopausal

Sex

• 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

Hematopoietic

• Not specified

Hepatic

• 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

Renal

• No unstable or uncompensated renal disease

Cardiovascular

• No unstable or uncompensated cardiac disease

Pulmonary

• No unstable or uncompensated pulmonary disease
• No clinically active interstitial lung disease
  • Asymptomatic chronic stable radiographic changes are allowed

Other

• 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

Expected Enrollment

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

Outcomes

Progression-free survival at 1 year

Tumor response as measured by RECIST
Duration of response as measured by RECIST
Safety as measured by CTC v2.0

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.

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Martine Piccart-Gebhart, MD, PhD, Study coordinator		Ph: 32-2-541-3206 Email: martine.piccart@bordet.be

Registry Information
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
Trial Start Date		2003-05-28
Registered in ClinicalTrials.gov		NCT00066378 1
Date Submitted to PDQ		2003-06-06
Information Last Verified		2006-11-19

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00066378