Metastatic Breast CancerPhase 2FLAGNCT01266213
Fulvestrant (F)/Goserelin (G) vs Anastrozole (A)/G vs G for Premenopausal Women
A Phase 2 study testing Fulvestrant plus Goserelin, Anastrozole plus Goserelin and Goserelin in people with Metastatic Breast Cancer and Estrogen Receptor Positive Tumor, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
Fulvestrant is an ER antagonist with no agonist effects, which binds, blocks and degrades the ER. Fulvestrant is comparable to third-generation aromatase inhibitors in terms of efficacy and tolerability for patients who have progressed on prior tamoxifen therapy and past studies have found all three-third-generation… Read more about this study
- Who is it for?
- Ages Up to 55 years, women only
- Conditions the study is for
- Metastatic Breast Cancer, Estrogen Receptor Positive Tumor, Breast Cancer Nos Premenopausal
- What is being tested?
- Fulvestrant plus Goserelin, Anastrozole plus Goserelin and Goserelin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 1 siteSouth Korea
- Study dates
- Dec 2010to Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Up to 55 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 1) All patients must be female and premenopausal. Premenopausal is defined as either: ① last menstrual period within 3 months, or ② post-hysterectomy without bilateral oophorectomy and with FSH in the premenopausal range (≤ 30 mIU/mL), or, ③ if on tamoxifen within the past 3 months, a plasma estradiol in the premenopausal range (≥20 pg/mL), ④ if in case of chemotherapy induced amenorrhea, a plasma estradiol in the premenopausal range (≥20 pg/mL).
- 2) Patients must have either positive estrogen and/or progesterone receptor determination by IHC or competitive binding assay on metastatic disease, or if not performed on their metastatic disease a positive result on their primary breast cancer specimen.
- 3) No HER2 overexpressing breast cancer by IHC 3+ or FISH. 4) Patients who showed progressive disease on tamoxifen treatment as a palliative hormonal therapy or an adjuvant endocrine treatment 5) Patients who recurred after 5 years of tamoxifen use and could not be considered for resume to tamoxifen treatment.
- 6) No prior treatment with an aromatase inhibitor or inactivator or fulvestrant 7) No prior treatment with an LH/RH agonist/antagonist except the use for ovarian protection for 6 months during adjuvant chemotherapy.
- 8) No adjuvant chemotherapy within 1 year of study entry. 9) Patients must have an ECOG performance status of 0, 1, or 2. 10) Patients must have adequate bone marrow, hepatic, and renal function 11) Patients must not have received chemotherapy or hormonal therapy for at least 4 weeks prior to enrollment.
- 12) Patients may receive irradiation to any bony sites of disease for pain control or for prevention of fracture.
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- 13) Patients may continue on bisphosphonates who already established on bisphosphonate therapy for at least 3 months.
- 14) Patients who are pregnant or lactating are ineligible. Must be using effective contraception or not be of childbearing potential.
- 15) Patients must not have had an active malignancy other than breast cancer, in situ carcinoma of the cervix, or non-melanomatous skin cancers in the past 5 years.
- 16) No active, unresolved infection. 17) All patients must give signed written informed consent
Who cannot join
- Patients who had received previous treatment for metastatic disease (including systemic cytostatic or hormonal treatment) other than tamoxifen.
- Lymphangitic pulmonary metastases
- Multiple or diffuse hepatic metastases
- Documented parenchymal or leptomeningeal brain metastasis
- HER-2 overexpressing breast cancer and concomitant trastuzumab treatment is not allowed
- Serious uncontrolled intercurrent infections
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- Serious intercurrent medical or psychiatric illness, including active cardiac disease
- Pregnancy or breast feeding
- Second primary malignancy (except in situ carcinoma of the cervix or resected papillary thyroid carcinoma or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Study OF Goserelin (G) Plus Fulvestrant (F) vs. G Plus Anastrozole (A)vs. G Alone for HR+, Tamoxifen Pretreated, Premenopausal Woman
Fulvestrant is an ER antagonist with no agonist effects, which binds, blocks and degrades the ER. Fulvestrant is comparable to third-generation aromatase inhibitors in terms of efficacy and tolerability for patients who have progressed on prior tamoxifen therapy and past studies have found all three-third-generation AIs to be at least as good as tamoxifen in first-line metastatic therapy in postmenopausal women. Fulvestrant has been studied little in premenopausal women despite of its attractive mechanism of actions. The clinical effectiveness of fulvestrant as a treatment for advanced breast cancer has previously been demonstrated at the standard dose (AD; 250 mg/mo) in several phase III clinical trials in postmenopausal women. However, there is evidence to suggest that doses of fulvestrant higher than 250 mg may have greater pharmacodynamic activity against the ER pathway. Moreover, dose-dependent clinical activity has been observed for fulvestrant. The activity of a fulvestrant high-dose (HD; 500 mg/mo) regimen has been investigated in two recent studies. A pilot Japanese study showed fulvestrant HD to have clinical activity in the treatment of advanced or recurrent breast cancer, to be well tolerated, and to result in plasma levels approximately double those seen with fulvestrant low-dose. Subsequently, a neoadjuvant study comparing fulvestrant low-dose and high-dose reported that significantly greater Ki67 and ER downregulation was achieved with the high-dose compared with the low-dose regimen and that both doses were well tolerated. A recent randomized trial also showed superior outcome of high-dose fulvestrant than AI.
Based on this rationale, we introduced high-dose fulvestrant with LHRH agonist as a randomized trial comparing with AI plus LHRH agonist and LHRH alone in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment.
Read the detailed description
This randomized phase II trial is studying fulvestrant with goserelin for ovarian suppression by goserelin to see how well it works compared to anastrozole with goserelin and goserelin alone in recurrent or metastatic ER-positive breast cancer.
- Conditions
- Metastatic Breast Cancer, Estrogen Receptor Positive Tumor, Breast Cancer Nos Premenopausal
- Being tested
- Fulvestrant plus Goserelin, Anastrozole plus Goserelin, Goserelin
- Keywords
- fulvestrant, anastrozole, goserelin, tamoxifen, premenopausal, hormone receptor positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fulvestrant plus GoserelinDrug
Also called Anastrozole plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Anastrozole plus GoserelinDrug
Also called Fulvestrant plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
GoserelinDrug
Also called Fulvestrant plus Goserelin, Anastrozole plus Goserelin
Goserelin s.c.
| Study group | Role | What they receive |
|---|---|---|
| Fulvestrant plus Goserelin | Experimental | Not described Receives: Drug: Fulvestrant plus Goserelin; Drug: Anastrozole plus Goserelin; Drug: Goserelin |
| Anastrozole plus Goserelin | Experimental | Not described Receives: Drug: Fulvestrant plus Goserelin; Drug: Anastrozole plus Goserelin; Drug: Goserelin |
| Goserelin alone | Active comparator | Not described Receives: Drug: Fulvestrant plus Goserelin; Drug: Anastrozole plus Goserelin; Drug: Goserelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (TTP)
To measure TTP, disease status will be measured every 3 cycles or clinically documented till progression
Measured: from the date of therapy to the date of progression every 3 months
Secondary outcomes (3)
overall response
Before start of 4th cycle of therapy, outcome measure will be perfomred to evaluate response
Measured: after 3 months from the first date of therapy
overall survival
from time to the first day of therapy to death
Measured: from the first date of therapy till death
Toxicity
Measured: from the first date of therapy to death every cycle of therapy (monthly)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionJun 2018 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 147 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Asan Medical Center, Seoul National University Hospital, Severance Hospital, Ulsan University Hospital, Kosin University Gospel Hospital, Korea University Guro Hospital, Korea University Anam Hospital
- Responsible party
- Principal investigator, Young-Hyuck Im, Samsung Medical Center
- Investigators
- Young-Hyuck Im, M.D., Ph.D., Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266213
- Sponsor's protocol ID
- 2010-04-001
- Acronym
- FLAG
- Status last verified
- Apr 2017
- First submitted
- 19 Dec 2010
- Last updated
- 1 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kim JY, Im SA, Jung KH, Ro J, Sohn J, Kim JH, Park YH, Kim TY, Kim SB, Lee KS, Kim GM, Kim SH, Kim S, Ahn JS, Lee KH, Ahn JH, Park IH, Im YH; breast cancer committee of Korean Cancer Study Group (KCSG). Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study). Eur J Cancer. 2018 Nov;103:127-136. doi: 10.1016/j.ejca.2018.08.004. Epub 2018 Sep 14.
PubMed 30223226
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study OF Goserelin (G) Plus Fulvestrant (F) vs. G Plus Anastrozole (A)vs. G Alone for HR+, Tamoxifen Pretreated, Premenopausal Woman
- ClinicalTrials.gov ID
- NCT01266213
- Acronym / sponsor ID
- FLAG / 2010-04-001
- Conditions
- Metastatic Breast Cancer, Estrogen Receptor Positive Tumor, Breast Cancer Nos Premenopausal
- Keywords
- fulvestrant, anastrozole, goserelin, tamoxifen, premenopausal, hormone receptor positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 147 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Collaborators
- Asan Medical Center, Seoul National University Hospital, Severance Hospital, Ulsan University Hospital, Kosin University Gospel Hospital, Korea University Guro Hospital, Korea University Anam Hospital
- Study start
- Dec 2010
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fulvestrant is an ER antagonist with no agonist effects, which binds, blocks and degrades the ER. Fulvestrant is comparable to third-generation aromatase inhibitors in terms of efficacy and tolerability for patients who have progressed on prior tamoxifen therapy and past studies have found all three-third-generation AIs to be at least as good as tamoxifen in first-line metastatic therapy in postmenopausal women. Fulvestrant has been studied little in premenopausal women despite of its attractive mechanism of actions. The clinical effectiveness of fulvestrant as a treatment for advanced breast cancer has previously been demonstrated at the standard dose (AD; 250 mg/mo) in several phase III clinical trials in postmenopausal women. However, there is evidence to suggest that doses of fulvestrant higher than 250 mg may have greater pharmacodynamic activity against the ER pathway. Moreover, dose-dependent clinical activity has been observed for fulvestrant. The activity of a fulvestrant high-dose (HD; 500 mg/mo) regimen has been investigated in two recent studies. A pilot Japanese study showed fulvestrant HD to have clinical activity in the treatment of advanced or recurrent breast cancer, to be well tolerated, and to result in plasma levels approximately double those seen with fulvestrant low-dose. Subsequently, a neoadjuvant study comparing fulvestrant low-dose and high-dose reported that significantly greater Ki67 and ER downregulation was achieved with the high-dose compared with the low-dose regimen and that both doses were well tolerated. A recent randomized trial also showed superior outcome of high-dose fulvestrant than AI.
Based on this rationale, we introduced high-dose fulvestrant with LHRH agonist as a randomized trial comparing with AI plus LHRH agonist and LHRH alone in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment.
Detailed description
This randomized phase II trial is studying fulvestrant with goserelin for ovarian suppression by goserelin to see how well it works compared to anastrozole with goserelin and goserelin alone in recurrent or metastatic ER-positive breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fulvestrant plus Goserelin | Experimental | Drug: Fulvestrant plus Goserelin, Drug: Anastrozole plus Goserelin, Drug: Goserelin |
| Anastrozole plus Goserelin | Experimental | Drug: Fulvestrant plus Goserelin, Drug: Anastrozole plus Goserelin, Drug: Goserelin |
| Goserelin alone | Active comparator | Drug: Fulvestrant plus Goserelin, Drug: Anastrozole plus Goserelin, Drug: Goserelin |
Who may qualify
- Ages
- Up to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 1) All patients must be female and premenopausal. Premenopausal is defined as either: ① last menstrual period within 3 months, or ② post-hysterectomy without bilateral oophorectomy and with FSH in the premenopausal range (≤ 30 mIU/mL), or, ③ if on tamoxifen within the past 3 months, a plasma estradiol in the premenopausal range (≥20 pg/mL), ④ if in case of chemotherapy induced amenorrhea, a plasma estradiol in the premenopausal range (≥20 pg/mL).
- 2) Patients must have either positive estrogen and/or progesterone receptor determination by IHC or competitive binding assay on metastatic disease, or if not performed on their metastatic disease a positive result on their primary breast cancer specimen.
- 3) No HER2 overexpressing breast cancer by IHC 3+ or FISH. 4) Patients who showed progressive disease on tamoxifen treatment as a palliative hormonal therapy or an adjuvant endocrine treatment 5) Patients who recurred after 5 years of tamoxifen use and could not be considered for resume to tamoxifen treatment.
- 6) No prior treatment with an aromatase inhibitor or inactivator or fulvestrant 7) No prior treatment with an LH/RH agonist/antagonist except the use for ovarian protection for 6 months during adjuvant chemotherapy.
- 8) No adjuvant chemotherapy within 1 year of study entry. 9) Patients must have an ECOG performance status of 0, 1, or 2. 10) Patients must have adequate bone marrow, hepatic, and renal function 11) Patients must not have received chemotherapy or hormonal therapy for at least 4 weeks prior to enrollment.
Key exclusion criteria (9 listed)
- Patients who had received previous treatment for metastatic disease (including systemic cytostatic or hormonal treatment) other than tamoxifen.
- Lymphangitic pulmonary metastases
- Multiple or diffuse hepatic metastases
- Documented parenchymal or leptomeningeal brain metastasis
- HER-2 overexpressing breast cancer and concomitant trastuzumab treatment is not allowed
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 |
|---|---|---|
| Fulvestrant plus GoserelinAlso: Anastrozole plus GoserelinFulvestrant s.c. plus Goserelin s.c. | Drug | Anastrozole plus Goserelin, Fulvestrant plus Goserelin, Goserelin alone |
| Anastrozole plus GoserelinAlso: Fulvestrant plus GoserelinAnastrozole 1 mg p.o. plus Goserelin s.c. | Drug | Anastrozole plus Goserelin, Fulvestrant plus Goserelin, Goserelin alone |
| GoserelinAlso: Fulvestrant plus Goserelin, Anastrozole plus GoserelinGoserelin s.c. | Drug | Anastrozole plus Goserelin, Fulvestrant plus Goserelin, Goserelin alone |
Primary outcome
Time to Progression (TTP)
Time frame: from the date of therapy to the date of progression every 3 months
To measure TTP, disease status will be measured every 3 cycles or clinically documented till progression
3 secondary outcomes
overall response
Time frame: after 3 months from the first date of therapy
overall survival
Time frame: from the first date of therapy till death
Toxicity
Time frame: from the first date of therapy to death every cycle of therapy (monthly)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2017.
- Derived from this study: PubMed 30223226Kim JY, Im SA, Jung KH, Ro J, Sohn J, Kim JH, Park YH, Kim TY, Kim SB, Lee KS, Kim GM, Kim SH, Kim S, Ahn JS, Lee KH, Ahn JH, Park IH, Im YH; breast cancer committee of Korean Cancer Study Group (KCSG). Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study). Eur J Cancer. 2018 Nov;103:127-136. doi: 10.1016/j.ejca.2018.08.004. Epub 2018 Sep 14.
- Korea Cancer Study GroupLink 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.
Young-Hyuck Im, M.D., Ph.D. principal investigator
Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fulvestrant plus Goserelin, Anastrozole plus Goserelin and Goserelin in people with Metastatic Breast Cancer and Estrogen Receptor Positive Tumor, run by Samsung Medical Center at 1 site in South Korea.
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 10 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 1 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Time to Progression (TTP) (time frame: from the date of therapy to the date of progression every 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01266213, which also lists 1 linked publication.
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 1 May 2017.