- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01300351
Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women
A Randomised, Double-Blind, Parallel-Group, Multicentre Study Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Postmenopausal Women With ER+ Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy
Study Overview
Detailed Description
Fulvestrant, at a dose of 250mg every 28 days, is the first oestrogen receptor antagonist with no agonist effects shown to be at least as effective for both TTP (Time to Progression) and OR (Objective Response) as a third-generation aromatase inhibitor in the second-line treatment of advanced breast cancer (Howell et al 2002, Osborne CK et al 2002).In these studies overall survival was also similar between the fulvestrant and anastrozole treatment arms (Pippen J et al 2003). Fulvestrant has received approval in 70 countries worldwide at this dose regimen.
However, evidence from a number of studies suggests that higher dose may be able to enhance efficacy further:
- Data from Study 0036 (Addo S et al, 2002) suggested that a dose-response relationship may exist. In female volunteers given a single intramuscular (i.m.) injection of fulvestrant (250mg, 125mg or placebo), there was a dose-dependent inhibition of ethinyloestradiol-induced endometrial thickening seen at Day 28.
- Results from short term exposure to fulvestrant in Studies 0002 (DeFriend D et al 1994) and 0018 (Robertson et al 2001) showed that expression of ER, progesterone receptor (PgR) and the cell proliferation-related antigen Ki67 are reduced in a dose-dependent manner.
- Data from Studies 0020 (Howell et al 2002) and 0021(Osborne CK et al 2002) suggested that a dose-response effect exists for fulvestrant. Fulvestrant 250mg was shown to be superior to fulvestrant 125mg, which was discontinued as it failed to meet minimum efficacy requirements.
- Evidence from pharmacokinetic modelling indicated that fulvestrant 500 mg dose regiment can achieve higher steady state plasma concentrations compared with fulvestrant 250mg and that steady state concentrations can be achieved earlier than with fulvestrant 250mg.
- Data from Study CONFIRM (A Di Leo et al 2009), a phase III randomised parallel-group trial, demonstrated that fulvestrant 500mg offers a statistically significant longer TTP compared with fulvestrant 250mg (median TTP: 6.5 months vs. 5.5 months; hazard ratio=0.80 [95% CI 0.68 to 0.94]; P=0.006), which seemed to be the consequence of an increase in the rate, and of a prolongation in duration, of disease stabilization. The 50% events overall survival analysis also seemed to favour fulvestrant 500mg, although statistical significance was not reached(hazard ratio=0.84 [95% CI 0.69 to 1.03]; P=0.091). The safety analysis did not raise any relevant concerns in relation to fulvestrant 500mg. Therefore, this study will compare Fulvestrant 500mg with fulvestrant 250mg in a Chinese population in order to understand the optimal dose for Chinese patients with breast cancer.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Beijing, China
- Research Site
-
Chongqing, China
- Research Site
-
Dalian, China
- Research Site
-
Guangzhou, China
- Research Site
-
Hangzhou, China
- Research Site
-
Harbin, China
- Research Site
-
Hefei, China
- Research Site
-
Jiangsu, China
- Research Site
-
Kunming, China
- Research Site
-
Nanning, China
- Research Site
-
Shandong, China
- Research Site
-
Shanghai, China
- Research Site
-
Shijiazhuang, China
- Research Site
-
Taiyuan, China
- Research Site
-
Tianjin, China
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Postmenopausal women defined as a woman who has stopped having menstrual periods
- Breast Cancer has continued to grow after having received treatment with an anti-estrogen hormonal treatment such as tamoxifen or an aromatase inhibitor
- Requiring hormonal treatment
- Oestrogen-receptor positive tumour
- Written informed consent to participate in the trial
Exclusion Criteria:
- Treatment with an investigational or non-approved drug within one month
- An existing serious disease, illness, or condition that will prevent participation or compliance with study procedures
- A history of allergies to any active or inactive ingredients of fulvestrant (i.e. castor oil)
- Treatment with more than one regimen of chemotherapy for advanced breast cancer
- Treatment with more than one regimen of hormonal treatment for advanced breast cancer
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Fulvestrant 500mg
Fulvestrant 500mg (2 syringes of Fulvestrant 250mg), Fulvestrant 500 mg i.m. every 28 (+/- 3) days plus an additional 500 mg on day 14 (+/-3) of first month only
|
Fulvestrant was supplied as a castor oil based solution in clear neutral glass pre-filled syringes.
Each syringe will contain 250 mg of fulvestrant in 5 ml.
Other Names:
|
ACTIVE_COMPARATOR: Fulvestrant 250mg
Fulvestrant 250mg (1 syringe of fulvestrant 250mg + 1 syringe matching placebo), Fulvestrant 250 mg and matching placebo i.m. every 28 (+/- 3) days plus an additional 2 placebo syringes on day 14 (+/-3) of first month only
|
Fulvestrant was supplied as a castor oil based solution in clear neutral glass pre-filled syringes.
Each syringe will contain 250 mg of fulvestrant in 5 ml.
Other Names:
Matching placebo was supplied as a castor oil based solution in clear neutral glass prefilled syringes.
Each syringe will contain 5 ml.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: 36 months
|
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of existing non-target lesions, or the appearance of new lesions, or death (by any cause in the absence of progression).
The primary analysis for PFS was the log rank test stratified by last endocrine therapy received prior to fulvestrant (AO vs. AI).
The treatment effect was estimated using the HR of 500 mg fulvestrant to 250 mg fulvestrant together with the corresponding 95% CI and p value.
|
36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate
Time Frame: 36 months
|
The ORR is defined as the proportion of all randomized patients with measurable disease at baseline who have a best objective tumour response of either CR or PR per RECIST v1.1.
|
36 months
|
Clinical Benefit Rate
Time Frame: 36 months
|
A clinical benefit (CB) responder is defined as a patient having a best overall response of either CR, PR or SD for at least 24 weeks per RECIST v1.1.
As tumour assessments can occur ± 2 weeks of the specified time point, the CBR is defined as the proportion of patients in the FAS who have CB ≥ 22 weeks (or 154 days).
|
36 months
|
Duration of Response
Time Frame: 36 months
|
Duration of response (DoR) will be evaluated only for patients who have an objective response, and is defined as the time from the date of first documentation of objective response (i.e., the initial visit at which CR or PR was recorded) until the date of disease progression or death due to any cause (whichever is earlier). The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. Any patient who has not progressed or died by the date of DCO, or who has been lost to follow up, will be right-censored at the date of their last disease assessment. |
36 months
|
Duration of Clinical Benefit
Time Frame: 36 months
|
Duration of clinical benefit (DoCB) will be evaluated only for patients who have CB, and is defined as the time from the date of randomisation until the date of disease progression or death from any cause, whichever is earlier. Any patient who has not progressed or died by the date of DCO or who has been lost to follow up will be right censored at the date of their last evaluable disease assessment. |
36 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Yuri E Rukazenkov, AstraZeneca
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D6997L00021
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Baylor Breast Care CenterRecruitingBreast Cancer | Breast Neoplasm | Triple Negative Breast Cancer | Triple Negative Breast Neoplasms | HER2-positive Breast Cancer | Breast Cancer Stage II | Breast Cancer Female | Breast Cancer Stage III | Estrogen Receptor-positive Breast Cancer | Hormone Receptor-positive Breast Cancer | Breast Cancer InvasiveUnited States
-
University of California, IrvineNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedBreast Cancer | HER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer | HER2-negative Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-positive Breast CancerUnited States
-
Joseph Baar, MD, PhDCompletedBreast Cancer | Stage I Breast Cancer | Inflammatory Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast CancerUnited States
-
Innocrin PharmaceuticalCompletedBreast Cancer | Advanced Breast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | Male Breast Cancer | ER+ Breast Cancer | Cancer of the BreastUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
Clinical Trials on Fulvestrant
-
Genor Biopharma Co., Ltd.RecruitingLocally Advanced or Metastatic Breast CancerChina
-
Ontario Clinical Oncology Group (OCOG)AstraZenecaCompleted
-
Xuanzhu Biopharmaceutical Co., Ltd.RecruitingAdvanced Breast CancerChina
-
Ahon Pharmaceutical Co., Ltd.RecruitingAdvanced Breast Cancer | Female Breast CancerChina
-
Jiangsu Hansoh Pharmaceutical Co., Ltd.Recruiting
-
Fudan UniversityActive, not recruiting
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Roswell Park Cancer InstituteCompleted
-
Zhejiang Cancer HospitalRecruitingBreast Neoplasm FemaleChina
-
European Organisation for Research and Treatment...Breast International GroupTerminatedBreast CancerUnited Kingdom