A Phase 3 interventional study of Fulvestrant and Placebo in Breast Cancer, sponsored by AstraZeneca. Completed at 15 sites in China. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-04-24.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
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.
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:
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This study's enrollment of 249 is above the median of 72 across 9,494 interventional studies indexed under Breast Neoplasms.
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Exclusion Criteria:
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
Drug: Fulvestrant
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
Drug: Fulvestrant · Drug: Placebo
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.
Also known as: Faslodex
Matching placebo was supplied as a castor oil based solution in clear neutral glass prefilled syringes. Each syringe will contain 5 ml.
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.
Time frame: 36 months
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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 36 months
The planned population size was 220 randomised patients. 249 patients were enrolled with 28 screen-failured patients and altogether 221 patients were randomised. The recuitment period of this study took 34 months, first subject in on 01 Mar 2011 and last subject in on 23 Dec 2013.
| Milestone | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| Started | 111 | 110 |
| Received study treatment | 109 | 110 |
| Completed | 75 | 72 |
| Not completed | 36 | 38 |
| Withdrew: Did not receive treatment | 2 | 0 |
| Withdrew: Ongoing treatment at data cut-off | 27 | 23 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Adverse event | 0 | 4 |
| Withdrew: Withdrawal by subject | 7 | 10 |
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.
| months | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| Progression-free Survival | 8.0 (2.8 to 16.6) | 4.0 (2.7 to 11.1) |
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.
| patients | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| Objective Response Rate | 16 (5.36 to 11.04) | 11 (2.92 to 5.72) |
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).
| patients | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| Clinical Benefit Rate | 53 | 36 |
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.
| months | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| Duration of Response | 16.6 (5.6 to NA) | 22.2 (10.8 to NA) |
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.
| months | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| Duration of Clinical Benefit | 14.3 (11.0 to 25.0) | 13.8 (11.0 to NA) |
Collected over Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fulvestrant 500 mg | — | 4/109 (3.7%) | 68/109 (62.4%) |
| Fulvestrant 250 mg | — | 9/110 (8.2%) | 65/110 (59.1%) |
| Event | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| PyrexiaGeneral disorders | 1/109 | 2/110 |
| Arthritis bacterialInfections and infestations | 0/109 | 2/110 |
| Hepatic function abnormalHepatobiliary disorders | 1/109 | 0/110 |
| Haemoglobin decreasedInvestigations | 1/109 | 1/110 |
| Bone painMusculoskeletal and connective tissue disorders | 1/109 | 0/110 |
| Cerebral infarctionNervous system disorders | 1/109 | 0/110 |
| AnaemiaBlood and lymphatic system disorders | 0/109 | 1/110 |
| Cardiac failureCardiac disorders | 0/109 | 1/110 |
| HypoglycaemiaMetabolism and nutrition disorders | 0/109 | 1/110 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/109 | 1/110 |
| Event | Fulvestrant 500 mg | Fulvestrant 250 mg |
|---|---|---|
| INJECTION SITE REACTIONGeneral disorders | 12/109 | 13/110 |
| PYREXIAGeneral disorders | 11/109 | 6/110 |
| INJECTION SITE PAINGeneral disorders | 8/109 | 10/110 |
| FATIGUEGeneral disorders | 9/109 | 7/110 |
| BACK PAINMusculoskeletal and connective tissue disorders | 8/109 | 4/110 |
| HEADACHENervous system disorders | 7/109 | 4/110 |
| NAUSEAGastrointestinal disorders | 6/109 | 7/110 |
| COUGHRespiratory, thoracic and mediastinal disorders | 2/109 | 6/110 |
| WHITE BLOOD CELL COUNT DECREASEDInvestigations | 5/109 | 2/110 |
| VOMITINGGastrointestinal disorders | 4/109 | 2/110 |
The planned population size was 220 randomised patients and altogether 221 patients were randomised. Key demographic and baseline characteristics were balanced between the treatment groups.
| Age, Continuous(years) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| Mean | 53.6 ± 10.12 | 53.1 ± 10.22 | 53.3 ± 10.15 |
| Age, Customized(participants) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| <50 Years | 37 | 40 | 77 |
| ≥50 to <65 Years | 61 | 56 | 117 |
| ≥65 Years | 13 | 14 | 27 |
| Sex: Female, Male(Participants) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| Female | 111 | 110 | 221 |
| Male | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| Asian | 111 | 110 | 221 |
| Weight(kg) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| Mean | 61.0 (35.0 to 85.0) | 60.5 (42.0 to 88.0) | 60.7 (35.0 to 88.0) |
| WHO Performance Status(participants) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| (0) Normal activity | 80 | 77 | 157 |
| (1) Restricted activity | 28 | 30 | 58 |
| (2) In bed ≤50% of the time | 3 | 3 | 6 |
| Extent of disease at baseline(participants) | Fulvestrant 500 mg | Fulvestrant 250 mg | Total |
|---|---|---|---|
| Locally advanced breast cancer only | 1 | 1 | 2 |
| Metastatic disease | 110 | 109 | 219 |
This study is completed, as verified in Apr 2015. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Fulvestrant