Thyroid Cancers Clinical Trial
Official title:
A Multicenter Phase II Pilot Open Label Study to Evaluate the Efficacy and Safety of BKM120 in the Treatment of Patients With Advanced or Metastatic Differentiated Thyroid Cancers
In France, 7-8 000 new thyroid cancer cases are diagnosed each year. Although a good overall
prognosis, it is usually estimated that 10 to 20% will rescue and 5% will become metastatic.
The standard treatment of advanced metastatic or recurrent thyroid cancer is limited to
radioiodine therapy. It is estimated that 30 to 50% of patients will become resistant to
radio iodine. Treatments options are limited in these refractory thyroid patients and long
term survival is estimated to less than 10%. Nowadays, no drug is approved in this
indication.
The recent explosion in knowledge in tumour biology and the identification of potential
biological targets in thyroid cancer led to several clinical trials with targeted therapies,
mainly focused on TKI inhibitors targeting the MAPkinase pathway and/or VEGF. Preliminary
results were encouraging in papillary thyroid tumors.
Follicular (FTC) and poorly differentiated thyroid (PDTC) cancers account for 10% of thyroid
cancer but 20-25% of cancers diagnosed at an advanced stage and near 50% of metastatic
refractory thyroid cancers. These cancers with an aggressive behavior represent a major
cause of death from thyroid cancer. In these subtypes, targeted therapies gave disappointing
results. This may be related to the mutational profile of these tumors which is different
from that of papillary cancers. Aberrant activation of the phosphatidylinositol-3-kinase
(PI3K)/AKT pathway is thought to play a fundamental role in thyroid tumorigenenesis of
follicular and poorly differentiated thyroid cancers. Many genetic alterations have been,
recently, identified in this pathway. PIK3CA mutations are found in 10-15% of FTC and can
also occur in metastases derived from PDTC. Amplification/genomic copy gain of the PIK3CA
has been identified in 24% of FTC and 42% of PDTC. Epigenetic inactivation of PTEN which
negatively regulates PI3K has been shown in FTC. Moreover, RAS mutations observed in 20-40%
of FTC and PDTC can activate the PI3K/AKT by interacting with the RAS-binding site of the
P110 catalytic subunit of PI3K.
Due to the high frequency of activation of PI3K and downstream effectors in progressive,
recurrent and poorly differentiated cancers, inhibition of the PI3K signaling pathway with
BKM120, a potent pan class I PI3K inhibitor, represents a particularly relevant therapeutic
target and should be properly evaluated in advanced follicular and poorly differentiated
thyroid carcinomas
The primary objective of the study will be to determine efficacy of BKM120 as measured by the progression free survival (PFS rate) at 6 months in patients with progressive, metastatic, refractory, follicular or poorly differentiated thyroid cancers. ;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment