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

• ClinicalTrials.gov Identifier: NCT01602380
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2012
• Results First Posted: May 17, 2017
• Last Update Posted: February 9, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: May 11, 2012
• First Posted Date: May 21, 2012
• Results First Submitted Date: March 23, 2017
• Results First Posted Date: May 17, 2017
• Last Update Posted Date: February 9, 2024
• Actual Study Start Date: October 17, 2012
• Actual Primary Completion Date: April 11, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2024)

Comparison of Progression-Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole [ Time Frame: 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) ]

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.

• Original Primary Outcome Measures (submitted: May 17, 2012): Compare the progression free survival (PFS) in patients treated with Fulvestrant with those treated with Anastrozole. [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease. ]

Current Secondary Outcome Measures (submitted: February 8, 2024)

• Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events [ Time Frame: 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 ]
  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.
• Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment [ Time Frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months) ]
  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.
• Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment [ Time Frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months) ]
  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.
• Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months) ]
  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).
• Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment [ Time Frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months) ]
  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.
• Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment [ Time Frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months) ]
  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.
• Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment [ Time Frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months) ]
  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).
• Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL) [ Time Frame: Quality of life questionnaires administered at 3 months post objective disease progression, then at 6-monthly intervals (approximately 75 months) ]
  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.

Original Secondary Outcome Measures (submitted: May 17, 2012)

• Compare the Overall Survival (OS, death due to any cause) in patients treated with Fulvestrant with those treated with Anastrozole when 50% of patients are recorded as having died. [ Time Frame: Following disease progression, patients will be contacted at 12 weekly intervals to determine survival status ]
• Measure objective response rate (ORR) for Fulvestrant treatment versus Anastrozole. (ORR =% of patients recording partial (PR) or complete response (CR). [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks ]
• Measure the duration of response (DoR) for Fulvestrant versus Anastrozole treatment. (DoR = days from PR/CR response to objective disease progression). [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks ]
• Measure expected duration of response (EDoR) for Fulvestrant treatment versus Anastrozole. (EDoR = p Efp(x), where x=DoR, p=proportion of responders, Efp(x) is mean duration of response). [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks ]
• Measure clinical benefit rate (CBR) for Fulvestrant treatment versus Anastrozole. (CBR= proportion of patients recording RECIST assessments of CR/PR or stable disease (SD) over at least 154 days. [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks ]
• Measure the duration of clinical benefit (DoCB) for Fulvestrant versus Anastrozole treatment. (DoCB = for patients recording clinical benefit responses only; days from randomization to date of disease progression). [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks ]
• Measure expected duration of clinical benefit (EDoCB) for Fulvestrant treatment versus Anastrozole. (EDoCB = p Efp(x), where x=DoCB, p=proportion of responders, Efp(x) is mean duration of clinical benefit). [ Time Frame: Baseline RECIST 1.1 assessments and then every 12 weeks ]
• Compare the effect of Fulvestrant treatment versus Anastrozole treatment on Health Related Quality of Life (HRQoL). [ Time Frame: Quality of life questionnaires completed at baseline, 12 weekly whilst on treatment, or 24 weekly for patients being followed for survival ]
• Compare the safety of fulvestrant versus anastrozole treatment by assessing adverse events and vital sign measurements: weight, pulse and blood pressure. [ Time Frame: Up to the primary analysis: Adverse events will be collected from date of consent to 56 days after final injection. Vital signs will be collected at each on-treatment visit and until 35 days after last injection ]
• Compare the safety of fulvestrant versus anastrozole treatment by assessing a panel of adverse events measures: electrocardiogram, haematology and clinical chemistry assessments. [ Time Frame: Up to the primary analysis: ECGs, clinical chemistry and haematology will be collected from randomization and every 12 weeks until 35 days after final injection. ]
• Compare the safety of fulvestrant versus anastrozole treatment after the primary analysis by continued collection and evaluation of serious adverse events. [ Time Frame: Following the primary analysis, only serious adverse events are recorded up until 56 days after a patient's final injection. ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Global Study to Compare the Effects of Fulvestrant and Arimidex in a Subset of Patients With Breast Cancer.
• 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.
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hormone Receptor Positive Breast Cancer

Intervention

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

Study Arms

• Experimental: faslodex+placebo
  Blinded: Fulvestrant 500mg intramuscular injection (2x250mg) plus dummy Anastrozole tablets
  Interventions:

  • Drug: faslodex 500mg
  • Drug: arimidex dummy
• Active Comparator: arimidex +placebo
  Blinded: Anastrozole 1mg tablets plus dummy Fulvestrant intramuscular injection (2x0mg)
  Interventions:

  • Drug: arimidex 1mg
  • Drug: faslodex dummy

Publications *

• Robertson JFR, Cheung KL, Noguchi S, Shao Z, Degboe A, Lichfield J, Thirlwell J, Fazal M, Ellis MJ. Health-related quality of life from the FALCON phase III randomised trial of fulvestrant 500 mg versus anastrozole for hormone receptor-positive advanced breast cancer. Eur J Cancer. 2018 May;94:206-215. doi: 10.1016/j.ejca.2018.02.026. Epub 2018 Mar 22.
• Robertson JFR, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. doi: 10.1016/S0140-6736(16)32389-3. Epub 2016 Nov 29.
• Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiowka M, Hewson N, Rukazenkov Y, Robertson JF. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study. J Clin Oncol. 2015 Nov 10;33(32):3781-7. doi: 10.1200/JCO.2015.61.5831. Epub 2015 Sep 14.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 30, 2017): 462
• Original Estimated Enrollment (submitted: May 17, 2012): 450
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: April 11, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Canada, China, Czechia, Italy, Japan, Mexico, Peru, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic, India

Administrative Information

• NCT Number: NCT01602380
• Other Study ID Numbers: D699BC00001; 2011-006326-24 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Shankar S, MD; AstraZeneca
• Principal Investigator: John Robertson, MD; Graduate Medicine and Health School, University of Nottingham, UK
• Principal Investigator: Matthew Ellis, DM; Washington University School of Medicine, USA

• PRS Account: AstraZeneca
• Verification Date: February 2024