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

Phase 3

Active, not recruiting

• Conditions: Hormone Receptor Positive Breast Cancer
• Interventions: Drug: arimidex 1mg; Drug: faslodex 500mg; Drug: faslodex dummy; Drug: arimidex dummy

• Registration Number: NCT01602380
• Lead Sponsor: AstraZeneca

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 Timeline

• Study First Submitted: 2012-05-11
• Study First Submitted QC: 2012-05-17
• Study First Posted: 2012-05-21
• Study Start: 2012-10-17
• Primary Completion: 2016-04-11
• Results First Submitted: 2017-03-23
• Results First Submitted QC: 2017-04-07
• Results First Posted: 2017-05-17
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-27
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 462

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
arimidex +placebo	arimidex 1mg	Blinded: Anastrozole 1mg tablets plus dummy Fulvestrant intramuscular injection (2x0mg)
arimidex +placebo	faslodex dummy	Blinded: Anastrozole 1mg tablets plus dummy Fulvestrant intramuscular injection (2x0mg)
faslodex+placebo	faslodex 500mg	Blinded: Fulvestrant 500mg intramuscular injection (2x250mg) plus dummy Anastrozole tablets
faslodex+placebo	arimidex dummy	Blinded: Fulvestrant 500mg intramuscular injection (2x250mg) plus dummy Anastrozole tablets

Primary Outcome Measures

Name	Time	Method
Comparison of Progression-Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment	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	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).
Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment	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 Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; 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	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	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.
Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment	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	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.
Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL)	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.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Stoke-on-Trent, United Kingdom