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

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 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.

Conditions

• Metastatic Breast Cancer
• Estrogen Receptor Positive Tumor
• Breast Cancer Nos Premenopausal

Interventions

DRUG

Fulvestrant plus Goserelin

Fulvestrant s.c. plus Goserelin s.c.

DRUG

Anastrozole plus Goserelin

Anastrozole 1 mg p.o. plus Goserelin s.c.

DRUG

Goserelin

Goserelin s.c.

Sponsors & Collaborators

• Asan Medical Center

  collaborator OTHER

• Seoul National University Hospital

  collaborator OTHER

• Severance Hospital

  collaborator OTHER

• Ulsan University Hospital

  collaborator OTHER

• Kosin University Gospel Hospital

  collaborator OTHER

• Korea University Guro Hospital

  collaborator OTHER

• Korea University Anam Hospital

  collaborator OTHER

• Samsung Medical Center

  lead OTHER

Principal Investigators

• Young-Hyuck Im, M.D., Ph.D. · Samsung Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

55 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-12-31

Primary Completion

2018-06-30

Completion

2019-12-31

Countries

• South Korea

Study Locations