Fulvestrant (Faslodex) + Anastrozole (Arimidex) vs Anastrozole

NCT ID: NCT00543127

Last Updated: 2023-03-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 870 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2016-07-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fulvestrant + Anastrozole

Fulvestrant loading dose regimen will consist of two 5 ml intramuscular injections on day 0 (500 mg), 250 mg single injection on days 14 and 28, and 250 mg single injection every 28 days thereafter for 3 years plus Anastrozole 1 mg PO once daily for 5 years

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

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

Intervention Type: DRUG

1 mg oral Anastrozole per day during 5 years.

Anastrozole

Anastrozole 1 mg will be administered orally as one tablet daily for 5 years.

Group Type: ACTIVE_COMPARATOR

Anastrozole

Intervention Type: DRUG

1 mg oral Anastrozole per day during 5 years.

Interventions

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.

Intervention Type: DRUG

Anastrozole

1 mg oral Anastrozole per day during 5 years.

Intervention Type: DRUG

Other Intervention Names

Faslodex; Arimidex

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Spanish Breast Cancer Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Hospital General Universitario Gregorio Marañón

Study Director

Role: STUDY_DIRECTOR

Centro Oncológico de Galicia

Study Director

Role: STUDY_DIRECTOR

Hospitales Universitarios Virgen del Rocío

Locations

Hospital Universitario Virgen de Los Lirios

Alcoy, Alicante, Spain

Hospital General Universitario de Elche

Elche, Alicante, Spain

Hospital General Universitario de Elda

Elda, Alicante, Spain

Hospital Usp San Jaime

Torrevieja, Alicante, Spain

Hospital de Torrevieja Salud Ute

Torrevieja, Alicante, Spain

Hospital Municipal de Badalona

Badalona, Barcelona, Spain

Hospital Universitari Germans Trias I Pujol

Badalona, Barcelona, Spain

Hospital General de Granollers

Granollers, Barcelona, Spain

Institut Catalá D'Oncología L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Hospital Mutua de Terrassa

Terrassa, Barcelona, Spain

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Consorcio Hospitalario Provincial de Castellón

Castellon, Castellón, Spain

Hospital Donostia

Donostia / San Sebastian, Guipúzcoa, Spain

Onkologikoa

Donostia / San Sebastian, Guipúzcoa, Spain

Hospital de Barbastro

Barbastro, Huesca, Spain

Complejo Hospitalario Universitario Insular-Materno Infantil

Las Palmas de Gran Canaria, LAS Palmas, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Hospital San Agustín de Avilés

Avilés, Principality of Asturias, Spain

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa CRUZ DE Tenerife, Spain

Hospital Universitario de Valme

Dos Hermanas, Sevilla, Spain

Hospital de Sagunto

Sagunto, Valencia, Spain

Hospital Lluís Alcanyis

Xátiva, Valencia, Spain

Hospital de Basurto

Bilbao, Vizcaya, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Centro Oncológico de Galicia

A Coruña, , Spain

Complejo Hospitalario Torrecárdenas

Almería, , Spain

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

Hospital Clinic I Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario Puerta Del Mar

Cadiz, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

HOSPITAL UNIVERSITARI DE GIRONA DR. JOSEP TRUETA (ICO de Girona)

Girona, , Spain

Hospital Universitario San Cecilio

Granada, , Spain

Hospital General Universitario de Guadalajara

Guadalajara, , Spain

Hospital Juan Ramón Jiménez

Huelva, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Ramón Y Cajal

Madrid, , Spain

Hospital Clínico Universitario San Carlos

Madrid, , Spain

CENTRO INTEGRAL ONCOLÓGICO CLARA CAMPAL (Hospital Madrid Norte Sanchinarro)

Madrid, , Spain

Hospital Clínico Universitario Virgen de La Victoria

Málaga, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, , Spain

Hospital Universitario Virgen Del Rocío

Seville, , Spain

Hospital Virgen de La Salud

Toledo, , Spain

Instituto Valenciano de Oncología

Valencia, , 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

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

Spain

References

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.

Reference Type: RESULT

PMID: 31152327 (View on PubMed)

Martin M, Carrasco E, Rodriguez-Lescure A, Andres R, Servitja S, Anton A, Ruiz-Borrego M, Bermejo B, Guerrero A, Ramos M, Santaballa A, Munoz M, Cruz J, Lopez-Tarruella S, Chacon JI, Alvarez I, Martinez P, Miralles JJ, Polonio O, Jara C, Aguiar-Bujanda D. Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Alamo IV registry. Breast Cancer Res Treat. 2023 Sep;201(2):151-159. doi: 10.1007/s10549-023-07002-1. Epub 2023 Jun 20.

Reference Type: DERIVED

PMID: 37338729 (View on PubMed)

Related Links

http://www.geicam.org

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

Other Identifiers

2007-003417-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEICAM/2006-10

Identifier Type: -

Identifier Source: org_study_id