Clinical trial NCT01300351: Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Advanced breast cancer
metastatic breast cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 249
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of a new dose of 500mg Fulvestrant with the standard dose of 250mg in Chinese postmenopausal women with oestrogen receptor positive advanced breast cancer who have failed a prior endocrine treatment.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival
timeFrame: 36 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 36 months
measure: Clinical Benefit Rate
timeFrame: 36 months
measure: Duration of Response
timeFrame: 36 months
measure: Duration of Clinical Benefit
timeFrame: 36 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jiangsu
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
Study officials:
affiliation: 307 Hospital of PLA
name: Zefei Jiang
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Yuri E Rukazenkov
role: STUDY_DIRECTOR
References: