Breast CancerPhase 3NCT01300351
Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women
A Phase 3 study testing Fulvestrant in people with Breast Cancer, run by AstraZeneca at 15 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Fulvestrant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 249 participants
- Where
- 15 sitesChina
- Study dates
- Mar 2011to Mar 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
China15 sites
Research Site
Beijing
Research Site
Chongqing
Research Site
Dalian
Research Site
Guangzhou
Research Site
Hangzhou
Research Site
Harbin
Research Site
Hefei
Research Site
Jiangsu
Research Site
Kunming
Research Site
Nanning
Research Site
Shandong
Research Site
Shanghai
Research Site
Shijiazhuang
Research Site
Taiyuan
Research Site
Tianjin
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Fulvestrant, Placebo
- Keywords
- Advanced breast cancer, metastatic breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
Also called Faslodex
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.
PlaceboDrug
Matching placebo was supplied as a castor oil based solution in clear neutral glass prefilled syringes. Each syringe will contain 5 ml.
| Study group | Role | What they receive |
|---|---|---|
| Fulvestrant 500mg | Experimental | 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 Receives: Drug: Fulvestrant |
| Fulvestrant 250mg | Active comparator | 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 Receives: Drug: Fulvestrant; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
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.
Measured: 36 months
Secondary outcomes (4)
Objective Response Rate
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.
Measured: 36 months
Clinical Benefit Rate
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).
Measured: 36 months
Duration of Response
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.
Measured: 36 months
Duration of Clinical Benefit
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.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zefei Jiang, Principal investigator, 307 Hospital of PLAYuri E Rukazenkov, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01300351
- Sponsor's protocol ID
- D6997L00021
- Status last verified
- Apr 2015
- First submitted
- 17 Feb 2011
- Last updated
- 24 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01300351
- Acronym / sponsor ID
- D6997L00021
- Conditions
- Breast Cancer
- Keywords
- Advanced breast cancer, metastatic breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 249 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 21 Feb 2011 (estimated)
- Results
- Posted 24 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fulvestrant 500mg | Experimental | Drug: FulvestrantFulvestrant 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 250mg | Active comparator | Drug: Fulvestrant, Drug: PlaceboFulvestrant 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FulvestrantAlso: FaslodexFulvestrant 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. | Drug | Fulvestrant 250mg, Fulvestrant 500mg |
| PlaceboMatching placebo was supplied as a castor oil based solution in clear neutral glass prefilled syringes. Each syringe will contain 5 ml. | Drug | Fulvestrant 250mg |
Primary outcome
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.
4 secondary outcomes
Objective Response Rate
Time frame: 36 months
Clinical Benefit Rate
Time frame: 36 months
Duration of Response
Time frame: 36 months
Duration of Clinical Benefit
Time frame: 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- D6997L00021\_CSR\_SynopsisLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zefei Jiang principal investigator
307 Hospital of PLA
Yuri E Rukazenkov study director
AstraZeneca
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fulvestrant in people with Breast Cancer, run by AstraZeneca at 15 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2015.