Exemestane Versus Anastrozole as First Line Hormone Therapy in Postmenopausal Metastatic Breast Cancer Patients

Study Overview
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Brief Summary
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This is a pivotal phase II, multicenter, open-label trial, designed to compare the efficacy of exemestane versus anastrozole as a first line treatment for advanced breast cancer. One hundred postmenopausal patients, with metastatic, positive hormone receptor breast cancer will be enrolled in this trial.

Detailed Description
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The primary study endpoint is objective response rate. The study has been designed following Simon's test, with a p1-p0=0.15. p1 is the optimum level of activity of the experimental treatment (exemestane), and p0 is the minimum expected activity. In this study, p1 is 25% (25% of RR) and p0 is 10% (10% of RR). With an alpha error of 0.05 and a beta error of 0.1, Simon test establishes a first step of 21 patients per treatment arm. If at least 2 objective responses are observed in exemestane arm, recruitment will continue until 100 patients have been recruited. After this second recruitment phase, at least 7 objective responses must be observed to confirm the expected exemestane level of activity.

Official Title
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Phase II Randomized, Multicenter, Crossover Clinical Trial for Administration of Exemestane vs. Anastrozole as First Line Treatment for Postmenopausal Patients With Hormone Receptor Positive Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Exemestane
* Drug: Anastrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological diagnoses of breast cancer. Postmenopausal women, defined as: Bilateral surgical oophorectomy or amenorrhoea >= 5 years; Age >= 56 years old and amenorrhoea >= 1 year; Chemotherapy induced amenorrhoea >= 2 years; Radiotherapy induced amenorrhoea at least 3 months before: Age < 56 and < 5 years of amenorrhoea: follicle-stimulating hormone (FSH) levels to confirm postmenopausal status. Metastatic breast cancer (stage IV) or non-operable locally advanced breast cancer (stage IIIB). Positive estrogen and/or progesterone receptors as >10% cells or >10fmol/mg. Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients who have received adjuvant tamoxifen are eligible, if progression has been established at least 24 months since treatment start. Neoadjuvant chemotherapy is allowed if progression has been established at least 12 months after end of treatment. Patients may have received a first line of chemotherapy for advanced disease, but treatment must have ended at least 4 weeks before enrolment, and all acute toxicities must be resolved. Previous treatment with Herceptin is allowed. Normal haematological, hepatic and renal functions. Performance status ECOG of 0, 1, 2. Life expectancy superior to 3 months. Written informed consent. Exclusion Criteria: Previous hormone treatment for metastatic disease. Previous treatment with aromatase inhibitors. Inflammatory breast cancer, or aggressive metastatic disease, or visceral lesions, or metastasis in the central nervous system (CNS). Non-measurable disease. Second malignancy except for basal skin carcinoma or cervical in situ carcinoma adequately treated. If other malignancies, patient must have a disease-free period superior to 5 years. Treatment with any investigational product in the 4 previous weeks. Patients with negative estrogen and progesterone receptor tumours.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exemestane<br>25mg/day per VO until progression disease, after this progression the patient could receive the another drug (comparator arm) ie Anastrozole by investigator decision | Drug: Anastrozole<br>* 1mg/day until progression disease<br>* Other names: Arimidex;|
| Active Comparator: Anastrozole<br>1mg/day per VO until progression disease, after this progression the patient could receive the another drug (experimental arm) ie Exemestane by investigator decision | Drug: Exemestane<br>* 25mg/day until progression disease<br>* Other names: Aromasil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) in both arms | Complete response plus partial response | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Time from last patient included to progression disease | From date of randomization until the date of new documented progression, assessed up to 24 months | 
| Time to progression after crossover | Time from crossover (2nd line) to progression disease | From date of crossover until the date of new documented progression, assessed up to 5 months | 
| Clinical benefit (1st line) | Completed response (CR) plus Partial Response (PR) plus Stable Diasease (SD) lasting ≥6 months | up to 6 months | 
| Clinical benefit after crossover (2nd line) | Completed response (CR) plus Partial Response (PR) plus Stable Diasease | up to 6 months | 
| Survival | Time from randomization of last patient included until death whatever cause. | up to 36 months | 
| Survival after crossover | Time from crossover until death whatever cause. | up to 24 months | 
| The Number of Participants Who Experienced Adverse Events (AE) | Patients who will receive at least one dose of Exemestane or Anastrozole will be evaluated for safety and toxicity. Safety will be assess by recording all clinical adverse events at each patient. | Until 30 days after the end of last patient study treatment (1st line) | 
| Toxicity after crossover | Patients who will receive at least one dose of Exemestane or Anastrozole will be evaluated for safety and toxicity. Safety will be assess by recording all clinical adverse events at each patient. | Until 30 days after the end of last patient study treatment (crossover: 2nd line) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic breast cancer, First line of hormone treatment, Postmenopausal women, Positive hormone receptor tumours