A Global Study to Compare the Effects of Fulvestrant and Arimidex in a Subset of Patients With Breast Cancer.

Hormone Receptor Positive Breast Cancer Clinical Trial

— FALCON  

Official title:

A Randomised, Double-blind, Parallel-group, Multicentre, Phase III Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX) 500 mg With Anastrozole (ARIMIDEX) 1 mg as Hormonal Treatment for Postmenopausal Women With Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Been Treated With Any Hormonal Therapy.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01602380
• Other study ID #: D699BC00001
• Secondary ID: 2011-006326-24
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 17, 2012
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare how treatment with Fulvestrant (FASLODEX) or Anastrozole (ARIMIDEX) effects disease progression for women with locally advanced or metastatic breast cancer who have not had prior hormonal treatment.

Description:

A Randomised, Double-blind, Parallel-group, Multicentre, Phase III Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX) 500 mg with Anastrozole (ARIMIDEX) 1 mg as Hormonal Treatment for Postmenopausal Women with Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Been Treated With Any Hormonal Therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 462
• Est. completion date: December 31, 2024
• Est. primary completion date: April 11, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Histological confirmation of breast cancer in post menopausal women (age >=60). Positive hormone receptor status (ER +ve and/or PgR +ve) of primary or metastatic tumour tissue based on local laboratory assessment.

• EITHER locally advanced disease (1 line of chemotherapy allowed only if remain unsuitable for therapy of curative intent) OR Metastatic disease. (1 line of chemotherapy for breast cancer allowed only if subsequent evidence of further progressive disease)

• At least 1 lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment.

• Postmenopausal women, fulfilling 1 of:

• Prior bilateral oophorectomy

• Age >60 years

• Age < 60 years and amenorrheic for 12+months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and FSH and oestradiol in the postmenopausal range

Exclusion Criteria:

• Presence of life-threatening metastatic disease

• Any of:

• Extensive hepatic involvement

• involving brain or meninges

• symptomatic pulmonary lymph spread

• Discrete lung metastases are acceptable if respiratory function is not significantly compromised

• Prior systemic therapy for breast cancer other than one line of cytotoxic chemotherapy (the last dose of chemotherapy must have been received more than 28 days prior to randomisation)

• Radiation therapy if not completed within 28 days prior to randomisation (with the exception of radiotherapy given for control of bone pain, started prior to randomisation). Prior hormonal treatment for breast cancer.

• Current or prior malignancy within previous 3 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix).

Related Conditions & MeSH terms

• Breast Neoplasms
• Hormone Receptor Positive Breast Cancer

Intervention

Drug:
• faslodex 500mg
2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter
• arimidex 1mg
oral tablet 1 daily
• faslodex dummy
2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter
• arimidex dummy
oral tablet 1 daily

Locations

Country	Name	City	State
Argentina	Research Site	La Rioja
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Pergamino
Argentina	Research Site	Rosario
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Santo Andre
Canada	Research Site	Abbotsford	British Columbia
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Thunder Bay	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Chengdu
China	Research Site	Dalian
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Suzhou
China	Research Site	Tianjin
Czechia	Research Site	Praha 5
Czechia	Research Site	Pribram
Italy	Research Site	Avellino
Italy	Research Site	Bari
Italy	Research Site	Benevento
Italy	Research Site	Catania
Italy	Research Site	Genova
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Treviglio
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Mitaka-shi
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Osaka-city
Japan	Research Site	Sakai-shi
Japan	Research Site	Suita-shi
Mexico	Research Site	Merida
Mexico	Research Site	Mexico, D.F.
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Katowice
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Romania	Research Site	Braila
Romania	Research Site	Craiova
Romania	Research Site	Onesti
Romania	Research Site	Timisoara
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	St-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Tomsk
Slovakia	Research Site	Bardejov
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Trencin
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape town
South Africa	Research Site	Cape Town
South Africa	Research Site	Pietermaritzburg
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Pamplona
Spain	Research Site	Pozuelo de Alarcon
Spain	Research Site	Sabadell
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Turkey	Research Site	Ankara
Turkey	Research Site	Gaziantep
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Mariupol
Ukraine	Research Site	Uzhhorod
Ukraine	Research Site	Vinnytsia
United Kingdom	Research Site	Airdrie
United Kingdom	Research Site	Derby
United Kingdom	Research Site	Stoke-on-Trent
United States	Research Site	Auburn	Maine
United States	Research Site	Columbus	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Memphis	Tennessee
United States	Research Site	Modesto	California
United States	Research Site	Montgomery	Ohio
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Savannah	Georgia
United States	Research Site	Somerset	New Jersey
United States	Research Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Czechia,  Italy,  Japan,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Progression-Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole	PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique.	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease (up to approximately 38 months)
Secondary	Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events	OS was defined as the time from randomisation until death by any cause. The current OS data correspond to that of the final analysis and the outcome measure is reported as percentage of patients with events.	Baseline (Day 0) up to data cut-off for final analysis (up to approximately 116 months). Following disease progression, patients were to be contacted at 12 weekly intervals to determine survival status
Secondary	Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment	ORR was defined as the percentage patients with an objective response (i.e. those recording a partial response [PR] or complete response [CR]) at some point during the study, prior to disease progression. ORR was assessed in patients with measurable disease at baseline only. The determination of measurable disease at baseline was done using baseline RECIST data. CR was disappearance of all target lesions since baseline; was any pathological lymph nodes selected as target lesions (TL) to have a reduction in short axis to <10 millimeter. PR was at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Secondary	Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment	DoR was defined only for patients who had an objective response, as the time in days from date of first documentation of response (CR/PR) until date of disease progression. CR was disappearance of all target lesions since baseline; any pathological lymph nodes selected as TL to have a reduction in short axis to <10 mm. At least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Secondary	Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment	EDoR was estimated using the formula EDoR = p Efp(x), where x = DoR, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65).	Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Secondary	Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment	CBR was defined as the percentage of patients who had a clinical benefit (i.e. best objective response of CR, PR or stable disease), that was maintained for at least 24 weeks, prior to any evidence of progression. Note that a minimum duration of 22 weeks for CBR was applicable in the analysis (rather than 24 weeks) to allow for the protocolled window of +/-2 weeks.	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Secondary	Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment	DoCB was defined only for patients who had clinical benefit, as the time in days from date of randomisation until the date of disease progression.	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Secondary	Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment	EDoCB was estimated using the formula EDoCB = p Efp(x), where x = EDoCB, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65).	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Secondary	Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL)	The Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire was the instrument selected to assess HRQoL and comprised of following subscales: physical well-being (PWB), functional well-being (FWB), social well-being, emotional well-being, and breast cancer subscale (BCS). The main outcome measure from the FACT-B questionnaire was the Trial Outcome Index (TOI), which was a summary of the following subscales: PWB, FWB, and BCS. Outcome measure is reported as median time to deterioration, defined as the interval from the date of baseline of final analysis to the first assessment of worsened without an improvement in the next 12 weeks in FACT-B TOI, or the date of death (by any cause in the absence of symptom deterioration). Time to deterioration as measured by FACT-B total score was derived similarly and is also reported.	Quality of life questionnaires administered at 3 months post objective disease progression, then at 6-monthly intervals (approximately 75 months)

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