Clinical trial NCT00543127: Fulvestrant (Faslodex) + Anastrozole (Arimidex) vs Anastrozole
Official title: Phase III Trial Comparing Efficacy and Tolerance of Fulvestrant for 3 Years (y) Combined With Anastrozole 5 y Versus Anastrozole 5 y as Adjuvant Hormonotherapy in Postmenopausal With Early Breast Cancer and Positive Hormone Receptors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: luminal
anastrozole
fulvestrant
early breast cancer
HR+/HER2-
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2007-10-12
Enrollment: 870
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Postmenopausal women with hormone receptor positive and negative Her2 tumours.

Before randomization, the patients will be stratified according to the center, positive nodes (0 vs. 1-3 vs. ≥4), previous chemotherapy (yes vs no) and hormonal receptors status.

Detailed description: It is expected that disease-free survival for patients receiving Anastrozole alone for 5 years will be up to 90%. An increase of 3% in disease-free survival (DFS) is expected in the arm of Fulvestrant plus Anastrozole, i.e a DFS of up to 93%. They will be required 1358 patients per treatment group (i.e, 2716 patients in total) to give 80% power, alfa bilateral 0.05, and OR 0.6888. Assuming 5% screening failures 2852 patients are required to enter the study. In Jun-2010 the recruitment was stopped due to lack of support of the financier based on the result of Faslodex® and Arimidex® in Combination Trial (FACT-trial), comparing Fulvestrant + Anastrozole vs Anastrozole alone in 1st relapse showed no difference in time to progression at more than 40 months follow-up.

Eligibility criteria: Inclusion criteria:

1. Histological documentation of breast cancer.
2. Stage I, II, IIIA and IIIC\* invasive breast cancer. One of these two characteristics must be fulfilled:

   * N+
   * T \> 1cm \*Eligible patients T1-T3 and pN3a (patients with metastasis in infraclavicular nodes would not be eligible)
3. Local treatment with curative intention:

   * mastectomy or tumour excision with free margins + radiotherapy
   * axillary lymphadenectomy or sentinel node biopsy
4. Positive hormone receptors (Estrogen Receptor \[ER\]+ and/or Progesterone Receptor \[PR\]+) in primary tumour tissue as measured by a central laboratory
5. Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, defined as immunohistochemistry (IHC) 0 or 1+ or negative fluorescence in situ hybridization (FISH) (in the event of IHC 2+ or 3+)
6. Postmenopausal women, defined as women meeting any of the following criteria:

   * Age ≥ 60 years
   * Age ≥ 45 years with amenorrhea ≥ 12 months in the moment of breast cancer diagnosis and an intact uterus
   * Prior bilateral ovariectomy
   * In case previous hysterectomy, follicle stimulating hormone (FSH) and estradiol levels within the postmenopausal range (using local laboratory ranges)\* \* In patients previously treated with a luteinizing hormone releasing hormone (LH-RH) analogue, the last extended release formulation should have been administered more than 6 months before randomisation, and menses must not have reappeared.
7. A World Health Organization (WHO) performance status of 0, 1, or 2.
8. Age \> 18 years

Exclusion criteria:

1. Presence of metastatic disease or bilateral invasive cancer
2. ER and Progesterone Receptor (PR) negative breast cancer
3. HER2-positive breast cancer, defined as FISH+
4. Treatment with a non-approved or experimental drug within 4 months of randomisation
5. Current malignancy or previous malignancy in the past 5 years (other that breast cancer or basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)
6. Pregnant or nursing patients
7. Any of the following laboratory values within 3 months of randomisation:

   * Platelets \< 100 x 109/L
   * Total bilirubin \> 1.5 x Upper limit of reference range (ULRR)\*\*

     \*\* Patients with documented Gilbert syndrome may be included in this trial
   * Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \> 2.5 x ULRR
   * A history of:
   * hemorrhagic diathesis (i.e. Disseminated Intravascular Coagulation \[DIC\], coagulation factor deficiency) or
   * long-term anticoagulant treatment (except for anti-platelet aggregants and low-dose warfarin; see section 3.7)
8. A history of hypersensitivity to the active ingredient or inactive excipients of fulvestrant, aromatase inhibitors, or castor oil
9. Any concomitant severe disease advising against patient participation in the trial o that may jeopardize compliance with the trial protocol, such as uncontrolled heart disease, uncontrolled diabetes mellitus, or uncontrolled severe infections
10. Hormone replacement therapy

Primary outcomes:
measure: Disease Free Survival (DFS) Events
timeFrame: Up to 5 years
Secondary outcomes:
measure: Breast Cancer Specific Survival (BCsS) Events
timeFrame: Up to 5 years
measure: Overall Survival (OS) Event
timeFrame: Up to 5 years
measure: Time to Recurrence (TR) Event
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Alcoy
country: Spain
facility: Hospital Universitario Virgen de Los Lirios
state: Alicante
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Elda
country: Spain
facility: Hospital General Universitario de Elda
state: Alicante
city: Torrevieja
country: Spain
facility: Hospital Usp San Jaime
state: Alicante
city: Torrevieja
country: Spain
facility: Hospital de Torrevieja Salud Ute
state: Alicante
city: Avilés
country: Spain
facility: Hospital San Agustín de Avilés
state: Asturias
city: Badalona
country: Spain
facility: Hospital Municipal de Badalona
state: Barcelona
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
state: Barcelona
city: Granollers
country: Spain
facility: Hospital General de Granollers
state: Barcelona
city: L'hospitalet de Llobregat
country: Spain
facility: Institut Catalá D'Oncología L'Hospitalet
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Castellón de La Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellón
state: Castellón
city: Donostia-san Sebastián
country: Spain
facility: Hospital Donostia
state: Guipúzcoa
city: Donostia-san Sebastián
country: Spain
facility: Onkologikoa
state: Guipúzcoa
city: Barbastro
country: Spain
facility: Hospital de Barbastro
state: Huesca
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular-Materno Infantil
state: LAS Palmas
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Santa CRUZ DE Tenerife
city: Dos Hermanas
country: Spain
facility: Hospital Universitario de Valme
state: Sevilla
city: Sagunto
country: Spain
facility: Hospital de Sagunto
state: Valencia
city: Xátiva
country: Spain
facility: Hospital Lluís Alcanyis
state: Valencia
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: A Coruña
country: Spain
facility: Centro Oncológico de Galicia
city: Almería
country: Spain
facility: Complejo Hospitalario Torrecárdenas
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta Del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Girona
country: Spain
facility: HOSPITAL UNIVERSITARI DE GIRONA DR. JOSEP TRUETA (ICO de Girona)
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Guadalajara
country: Spain
facility: Hospital General Universitario de Guadalajara
city: Huelva
country: Spain
facility: Hospital Juan Ramón Jiménez
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón Y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Madrid
country: Spain
facility: CENTRO INTEGRAL ONCOLÓGICO CLARA CAMPAL (Hospital Madrid Norte Sanchinarro)
city: Malaga
country: Spain
facility: Hospital Clínico Universitario Virgen de La Victoria
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de Candelaria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocío
city: Toledo
country: Spain
facility: Hospital Virgen de La Salud
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital General Universitario Gregorio Marañón
name: Study Director
role: STUDY_DIRECTOR
affiliation: Centro Oncológico de Galicia
name: Study Director
role: STUDY_DIRECTOR
affiliation: Hospitales Universitarios Virgen del Rocío
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Ruiz-Borrego M, Guerrero-Zotano A, Bermejo B, Ramos M, Cruz J, Baena-Canada JM, Cirauqui B, Rodriguez-Lescure A, Alba E, Martinez-Janez N, Munoz M, Antolin S, Alvarez I, Del Barco S, Sevillano E, Chacon JI, Anton A, Escudero MJ, Ruiz V, Carrasco E, Martin M; GEICAM. Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study. Breast Cancer Res Treat. 2019 Aug;177(1):115-125. doi: 10.1007/s10549-019-05296-8. Epub 2019 May 31.