Fulvestrant (F)/Goserelin (G) vs Anastrozole (A)/G vs G for Premenopausal Women
Status:
Unknown status
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 2
Details
Lead Sponsor:
Samsung Medical Center
Collaborators:
Asan Medical Center Korea University Anam Hospital Korea University Guro Hospital Kosin University Gospel Hospital Seoul National University Hospital Severance Hospital Ulsan University Hospital