Clinical trial NCT00128843: Exemestane Versus Anastrozole as First Line Hormone Therapy in Postmenopausal Metastatic Breast Cancer Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Metastatic breast cancer
First line of hormone treatment
Postmenopausal women
Positive hormone receptor tumours
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2005-08-10
Enrollment: 103
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR) in both arms
timeFrame: up to 12 months
Secondary outcomes:
measure: Time to progression
timeFrame: From date of randomization until the date of new documented progression, assessed up to 24 months
measure: Time to progression after crossover
timeFrame: From date of crossover until the date of new documented progression, assessed up to 5 months
measure: Clinical benefit (1st line)
timeFrame: up to 6 months
measure: Clinical benefit after crossover (2nd line)
timeFrame: up to 6 months
measure: Survival
timeFrame: up to 36 months
measure: Survival after crossover
timeFrame: up to 24 months
measure: The Number of Participants Who Experienced Adverse Events (AE)
timeFrame: Until 30 days after the end of last patient study treatment (1st line)
measure: Toxicity after crossover
timeFrame: Until 30 days after the end of last patient study treatment (crossover: 2nd line)
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol
state: Barcelona
city: A Coruña
country: Spain
facility: Clínico Universitario A Coruña (CHUAC)
state: Galicia
city: Donostia-San Sebastián
country: Spain
facility: Onkologikoa
state: Guipúzcoa
city: Donostia-San Sebastián
country: Spain
facility: Hospital Donostia
state: Guipúzcoa
city: Barbastro
country: Spain
facility: H Comarcal de Barbastro
state: Huesca
city: Sagunto
country: Spain
facility: H Puerto de Sagunto
state: Valencia
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Madrid
country: Spain
facility: Puerta de Hierro
city: Madrid
country: Spain
facility: Ruber Internacional
city: Tarragona
country: Spain
facility: H Sant Camil
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología (IVO)
city: Zaragoza
country: Spain
facility: Clínico Lozano Blesa
city: Zaragoza
country: Spain
facility: H Universitario Miguel Servet
Study officials:
affiliation: Instituto Valenciano de Oncología
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Llombart-Cussac A, Ruiz A, Anton A, Barnadas A, Antolin S, Ales-Martinez JE, Alvarez I, Andres R, Garcia Saenz JA, Lao J, Carrasco E, Camara C, Casas I, Martin M. Exemestane versus anastrozole as front-line endocrine therapy in postmenopausal patients with hormone receptor-positive, advanced breast cancer: final results from the Spanish Breast Cancer Group 2001-03 phase 2 randomized trial. Cancer. 2012 Jan 1;118(1):241-7. doi: 10.1002/cncr.26299. Epub 2011 Jun 29.