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

NCT ID: NCT00066378

Last Updated: 2013-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

• 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.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

anastrozole

Intervention Type: DRUG

gefitinib

Intervention Type: DRUG

Arimidex + Placebo

Treatment should be administered until documented disease progression, unacceptable toxicity as judged by the responsible physician or patient refusal

Group Type: ACTIVE_COMPARATOR

anastrozole

Intervention Type: DRUG

Interventions

anastrozole

Intervention Type: DRUG

gefitinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

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

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martine J. Piccart, MD, PhD

Role: STUDY_CHAIR

Jules Bordet Institute

Locations

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Algemeen Ziekenhuis Sint-Augustinus

Wilrijk, , Belgium

Institut Bergonie

Bordeaux, , France

Centre Henri Becquerel

Rouen, , France

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Institute of Oncology - Ljubljana

Ljubljana, , Slovenia

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, United Kingdom

Countries

Belgium; France; Netherlands; Slovenia; United Kingdom

References

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.

Reference Type: RESULT

Tryfonidis K, Basaran G, Bogaerts J, Debled M, Dirix L, Thery JC, Tjan-Heijnen VC, Van den Weyngaert D, Cufer T, Piccart M, Cameron D; EORTC-Breast Cancer Group. A European Organisation for Research and Treatment of Cancer randomized, double-blind, placebo-controlled, multicentre phase II trial of anastrozole in combination with gefitinib or placebo in hormone receptor-positive advanced breast cancer (NCT00066378). Eur J Cancer. 2016 Jan;53:144-54. doi: 10.1016/j.ejca.2015.10.012. Epub 2015 Dec 24.

Reference Type: DERIVED

PMID: 26724641 (View on PubMed)

Other Identifiers

EORTC-10021

Identifier Type: -

Identifier Source: secondary_id

IDBBC-10021

Identifier Type: -

Identifier Source: secondary_id

EORTC-10021

Identifier Type: -

Identifier Source: org_study_id