Breast Cancer
Conditions
Keywords
Metastatic breast cancer, First line of hormone treatment, Postmenopausal women, Positive hormone receptor tumours
Brief summary
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
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.
Interventions
DRUGExemestane
25mg/day until progression disease
DRUGAnastrozole
1mg/day until progression disease
Sponsors
Pfizer
Spanish Breast Cancer Research Group
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in both arms | up to 12 months | Complete response plus partial response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression after crossover | From date of crossover until the date of new documented progression, assessed up to 5 months | Time from crossover (2nd line) to progression disease |
| Clinical benefit (1st line) | up to 6 months | Completed response (CR) plus Partial Response (PR) plus Stable Diasease (SD) lasting ≥6 months |
| Clinical benefit after crossover (2nd line) | up to 6 months | Completed response (CR) plus Partial Response (PR) plus Stable Diasease |
| Time to progression | From date of randomization until the date of new documented progression, assessed up to 24 months | Time from last patient included to progression disease |
| Survival after crossover | up to 24 months | Time from crossover until death whatever cause. |
| The Number of Participants Who Experienced Adverse Events (AE) | Until 30 days after the end of last patient study treatment (1st line) | 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. |
| Toxicity after crossover | Until 30 days after the end of last patient study treatment (crossover: 2nd line) | 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. |
| Survival | up to 36 months | Time from randomization of last patient included until death whatever cause. |
Countries
Spain
Outcome results
None listed