Fulvestrant (F)/Goserelin (G) vs Anastrozole (A)/G vs G for Premenopausal Women (FLAG)

April 27, 2017 updated by: Young-Hyuck Im, Samsung Medical Center

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.

Study Overview

Status

Unknown

Conditions

Intervention / 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 Type

Interventional

Enrollment (Anticipated)

147

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 53 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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.

    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

Exclusion Criteria:

  1. Patients who had received previous treatment for metastatic disease (including systemic cytostatic or hormonal treatment) other than tamoxifen.
  2. Lymphangitic pulmonary metastases
  3. Multiple or diffuse hepatic metastases
  4. Documented parenchymal or leptomeningeal brain metastasis
  5. HER-2 overexpressing breast cancer and concomitant trastuzumab treatment is not allowed
  6. Serious uncontrolled intercurrent infections
  7. Serious intercurrent medical or psychiatric illness, including active cardiac disease
  8. Pregnancy or breast feeding
  9. 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fulvestrant plus Goserelin
Drug: Fulvestrant plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Other Names:
  • Anastrozole plus Goserelin
Drug: Anastrozole plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
Other Names:
  • Fulvestrant plus Goserelin
Drug: Goserelin
Goserelin s.c.
Other Names:
  • Anastrozole plus Goserelin
  • Fulvestrant plus Goserelin
Experimental: Anastrozole plus Goserelin
Drug: Fulvestrant plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Other Names:
  • Anastrozole plus Goserelin
Drug: Anastrozole plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
Other Names:
  • Fulvestrant plus Goserelin
Drug: Goserelin
Goserelin s.c.
Other Names:
  • Anastrozole plus Goserelin
  • Fulvestrant plus Goserelin
Active Comparator: Goserelin alone
Drug: Fulvestrant plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Other Names:
  • Anastrozole plus Goserelin
Drug: Anastrozole plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
Other Names:
  • Fulvestrant plus Goserelin
Drug: Goserelin
Goserelin s.c.
Other Names:
  • Anastrozole plus Goserelin
  • Fulvestrant plus Goserelin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
from the date of therapy to the date of progression every 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall response
Time Frame: after 3 months from the first date of therapy
Before start of 4th cycle of therapy, outcome measure will be perfomred to evaluate response
after 3 months from the first date of therapy
overall survival
Time Frame: from the first date of therapy till death
from time to the first day of therapy to death
from the first date of therapy till death
Toxicity
Time Frame: from the first date of therapy to death every cycle of therapy (monthly)
from the first date of therapy to death every cycle of therapy (monthly)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Collaborators

Asan Medical Center
Seoul National University Hospital
Ulsan University Hospital
Korea University Anam Hospital
Korea University Guro Hospital
Severance Hospital
Kosin University Gospel Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (Anticipated)

June 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

December 19, 2010

First Submitted That Met QC Criteria

December 22, 2010

First Posted (Estimate)

December 24, 2010

Study Record Updates

Last Update Posted (Actual)

May 1, 2017

Last Update Submitted That Met QC Criteria

April 27, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-04-001

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.

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