Comparing Anastrozole-Placebo to the Combination Anastrozole-ZD1839 in Postmenopausal Patients With Estrogen Receptor and/or Progesterone Receptor Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study is being carried out to see if treatment with ZD1839 (Gefitinib) combined with Arimidex (Anastrozole) has improved efficacy over Arimidex alone in preventing progression of metastatic breast cancer.

Detailed Description
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This is a phase II, multicenter, double-blind, randomized, placebo-controlled trial. Patients will be randomized in a double-blind manner in a 1:1 ratio to receive either 250 mg/day ZD1839 or matched placebo in combination with 1 mg/day anastrozole. The dose of ZD1839 has been selected based on clinical studies in other tumor types suggesting identical efficacy together with a better toxicity profile in patients treated at 250 mg compared to 500 mg/day. The 1 mg dose of anastrozole is the standard approved dose.

Official Title
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Phase II Multicenter, Double-Blind, Randomized Trial Comparing Anastrozole (ZD1033, Arimidex™)-Placebo to the Combination Anastrozole-ZD1839 (Gefitinib, IRESSA™) in Postmenopausal Patients With Estrogen Receptor (ER) and/or Progesterone Receptor (PgR) Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Gefitinib
* Drug: Anastrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female postmenopausal patients aged 18 years or older with newly diagnosed metastatic breast cancer. Patients with recurrent disease during or after adjuvant tamoxifen or patients who are hormone therapy naïve are eligible for this trial. A paraffin embedded tumor tissue block or slides from either the metastatic or primary tumor site is required. Exclusion Criteria: Patients cannot be on hormone replacement therapy while on study. Prior chemotherapy received for metastatic disease is not allowed. Previous treatment with tyrosine kinase inhibitors or aromatase inhibitors is not allowed. Patients who have evidence of an active interstitial lung disease are not eligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anastrozole-placebo<br>Anastrozole (ZD1033, Arimidex)-Placebo | Drug: Anastrozole<br>* 1 mg Anastrozole (ZD1033, Arimidex) + PLACEBO 1 TABLET/DAY PO<br>* Other names: Arimidex;|
| Active Comparator: Anastrozole-ZD1839<br>Anastrozole (ZD1033, Arimidex)-ZD1839 (gefitinib, IRESSA) | Drug: Gefitinib<br>* ZD1839 (gefitinib, IRESSA) 250 mg/DAY PO + 1 mg Anastrozole (ZD1033, Arimidex)<br>* Other names: IRESSA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | To estimate TTP in the 2 treatment arms of postmenopausal patients with newly diagnosed metastatic breast cancer | Duration of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | To estimate the ORR (complete response [CR] and partial response [PR] as defined by RECIST for the 2 treatment arms | Duration of Study | 
| Overall clinical benefit rate | To estimate the clinical benefit rates (CBR; defined as CR+PR[as per RECIST]+stable disease [SD]>24 weeks) for the 2 treatment arms | Duration of Study | 
| Overall survival | To estimate overall survival (OS) for each of the 2 treatment arms | Duration of Study | 
| Safety | To compare the tolerability of anastrozole/placebo to that of anastrozole/ZD1839 | Duration of Study | 
| Pharmacokinetic variables | To determine steady-state plasma trough concentrations of anastrozole in all patients. To determine steady-state trough concentrations of ZD1839 and to relate values to historical data | Duration of Study | 
| Biomarker objectives | To obtain tumor tissue and blood samples for biologic studies in the limited population available and measure expression of markers that may potentially correlate with response to treatment in this patient population | Duration of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic breast cancer