Fulvestrant (Faslodex) + Anastrozole (Arimidex) vs Anastrozole

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00543127
• Other study ID #: GEICAM/2006-10
• Secondary ID: 2007-003417-14
• Status: Terminated
• Phase: Phase 3
• Start date: November 2007
• Est. completion date: July 2016

Study information

• Verified date: March 2023
• Source: Spanish Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 870
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fulvestrant
500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.
• Anastrozole
1 mg oral Anastrozole per day during 5 years.

Locations

Country	Name	City	State
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Universitario Virgen de Los Lirios	Alcoy	Alicante
Spain	Complejo Hospitalario Torrecárdenas	Almería
Spain	Hospital San Agustín de Avilés	Avilés	Asturias
Spain	Hospital Municipal de Badalona	Badalona	Barcelona
Spain	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona
Spain	Hospital de Barbastro	Barbastro	Huesca
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Hospital Universitario Puerta Del Mar	Cadiz
Spain	Consorcio Hospitalario Provincial de Castellón	Castellón de La Plana	Castellón
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Donostia	Donostia-san Sebastián	Guipúzcoa
Spain	Onkologikoa	Donostia-san Sebastián	Guipúzcoa
Spain	Hospital Universitario de Valme	Dos Hermanas	Sevilla
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital General Universitario de Elda	Elda	Alicante
Spain	HOSPITAL UNIVERSITARI DE GIRONA DR. JOSEP TRUETA (ICO de Girona)	Girona
Spain	Hospital Universitario San Cecilio	Granada
Spain	Hospital General de Granollers	Granollers	Barcelona
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Hospital Juan Ramón Jiménez	Huelva
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Institut Catalá D'Oncología L'Hospitalet	L'hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de Canarias	La Laguna	Santa CRUZ DE Tenerife
Spain	Complejo Hospitalario Universitario Insular-Materno Infantil	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Universitario Arnau de Vilanova de Lleida	Lleida
Spain	CENTRO INTEGRAL ONCOLÓGICO CLARA CAMPAL (Hospital Madrid Norte Sanchinarro)	Madrid
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Ramón Y Cajal	Madrid
Spain	Hospital Clínico Universitario Virgen de La Victoria	Malaga
Spain	Hospital Regional Universitario Carlos Haya	Malaga
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona
Spain	Hospital de Sagunto	Sagunto	Valencia
Spain	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz de Tenerife
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen Del Rocío	Sevilla
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Virgen de La Salud	Toledo
Spain	Hospital de Torrevieja Salud Ute	Torrevieja	Alicante
Spain	Hospital Usp San Jaime	Torrevieja	Alicante
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Arnau de Vilanova de Valencia	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Hospital Lluís Alcanyis	Xátiva	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	AstraZeneca

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival (DFS) Events	Disease-free survival (DFS) has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.; DFS event is defined as the evidence of local and/or distant recurrence, new primary breast tumour, or death from any cause.	Up to 5 years
Secondary	Breast Cancer Specific Survival (BCsS) Events	BCsS events has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to BCsS in patients treated with anastrozole for 5 years.; BCsS event is defined as the death from breast cancer.	Up to 5 years
Secondary	Overall Survival (OS) Event	OS event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.; OS event is defined as the death from any cause.	Up to 5 years
Secondary	Time to Recurrence (TR) Event	TR event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.; TR event is defined as the evidence of breast cancer recurrence (local and/or distant recurrence of breast cancer, does not include second primary malignancies or deaths from any cause).	Up to 5 years

External Links

•   Description Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group