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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2011 by Samsung Medical Center
Sponsor:
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
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01266213
First received: December 19, 2010
Last updated: July 26, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Estrogen Receptor Positive Tumor
Breast Cancer Nos Premenopausal
Drug: Fulvestrant plus Goserelin
Drug: Anastrozole plus Goserelin
Drug: Goserelin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: from the date of therapy to the date of progression every 3 months ] [ Designated as safety issue: Yes ]
    To measure TTP, disease status will be measured every 3 cycles or clinically documented till progression


Secondary Outcome Measures:
  • overall response [ Time Frame: after 3 months from the first date of therapy ] [ Designated as safety issue: Yes ]
    Before start of 4th cycle of therapy, outcome measure will be perfomred to evaluate response

  • overall survival [ Time Frame: from the first date of therapy till death ] [ Designated as safety issue: Yes ]
    from time to the first day of therapy to death

  • Toxicity [ Time Frame: from the first date of therapy to death every cycle of therapy (monthly) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 147
Study Start Date: December 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fulvestrant plus Goserelin Drug: Fulvestrant plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Other Name: Anastrozole plus Goserelin
Drug: Anastrozole plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
Other Name: Fulvestrant plus Goserelin
Drug: Goserelin
Goserelin s.c.
Other Names:
  • Fulvestrant plus Goserelin
  • Anastrozole plus Goserelin
Experimental: Anastrozole plus Goserelin Drug: Fulvestrant plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Other Name: Anastrozole plus Goserelin
Drug: Anastrozole plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
Other Name: Fulvestrant plus Goserelin
Drug: Goserelin
Goserelin s.c.
Other Names:
  • Fulvestrant plus Goserelin
  • Anastrozole plus Goserelin
Active Comparator: Goserelin alone Drug: Fulvestrant plus Goserelin
Fulvestrant s.c. plus Goserelin s.c.
Other Name: Anastrozole plus Goserelin
Drug: Anastrozole plus Goserelin
Anastrozole 1 mg p.o. plus Goserelin s.c.
Other Name: Fulvestrant plus Goserelin
Drug: Goserelin
Goserelin s.c.
Other Names:
  • Fulvestrant plus Goserelin
  • Anastrozole plus Goserelin

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.

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01266213

Contacts
Contact: Yeon Hee Park, M.D. 82-2-3410-1780 yhparkhmo@skku.edu
Contact: Young-Hyuck Im, M.D. 82-2-3410-3445 imyh00@skku.edu

Locations
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Yeon Hee Park, M.D.    82-2-3410-1780    yhparkhmo@skku.edu   
Sub-Investigator: Yeon Hee Park, M.D.         
Sub-Investigator: Jin Seok Ahn, M.D.         
Sub-Investigator: Jong Mu Sun, M.D.         
Principal Investigator: Young-Hyuck Im, M.D.         
Sponsors and Collaborators
Samsung Medical Center
Asan Medical Center
Seoul National University Hospital
Severance Hospital
Ulsan University Hospital
Kosin University Gospel Hospital
Korea University Guro Hospital
Korea University Anam Hospital
Investigators
Principal Investigator: Young-Hyuck Im, M.D., Ph.D. Samsung Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Young-Hyuck Im/Professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01266213     History of Changes
Other Study ID Numbers: 2010-04-001
Study First Received: December 19, 2010
Last Updated: July 26, 2011
Health Authority: Korea: Food and Drug Administration

Keywords provided by Samsung Medical Center:
fulvestrant
anastrozole
goserelin
tamoxifen
premenopausal
hormone receptor positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Goserelin
Fulvestrant
Anastrozole
Estradiol
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Hormones
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014