A Phase I ,Single Center, Open-labeling, Single and Dose-escalating Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of Oral Novel ERa36 Modifier Icaritin in Advanced Breast Patients
ERa36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a
membrane-initiated "nongenomic" signaling pathway. Membrane-initiated estrogen signaling has
been linked to rapid responses to estrogen and generally activates signaling pathways like
MAPK/ERK, phosphatidylinositol-3-kinase, and protein kinase C pathways. Preclinical study
demonstrated that ERa36 was expressed in tumor cells and might be the driving force of
breast cancer cell proliferation. 40% of breast cancer tumors which used to be considered as
ER negative also express ERa36. In the former study the investigators found that 40% of
ERa66-positive breast cancer patients express high levels of ERa36 in their tumors, and this
subset of patients are less likely to benefit from tamoxifen treatment compared with those
with ERa66-positive/ERa36-negative tumors.
Icaritin is a newly discovered small molecular compound which is high selective ERa36
modulators and perhaps will be a very promising new drug to treat advanced breast cancer by
targeting this nongenomic pathway. It was showed that it can inhibit the growth of breast
cancer cells both in vitro and in vivo. The investigators have completed the preclinical
PK&PD and toxicity studies in animals and now move on to test it in a FIM clinical trial.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess safety of icaritin in breast cancer patients
to find the dose-limiting toxicity(DLT)and maximal tolerated dose(MTD)of icaritin in breast cancer patients
1-2 YEAR
Yes
Binghe Xu, MD
Principal Investigator
Cancer Institute Hospital, Chinese Academy of Medical Sciences
China: Food and Drug Administration
TG0929ICR
NCT01278810
November 2010
December 2011
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