MedTrace Logo

A Multicenter Phase II Pilot Open Label

NCT01830504 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 47

Last updated 2016-10-05

No results posted yet for this study

Summary

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

Conditions

  • Thyroid Cancers

Interventions

DRUG

BKM120

BKM 120, 100 mg/day continuously. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are permitted in order to allow the patient to continue the study treatment. Dose level -1 : 80 mg/day continuously, Dose level -2 : 80 mg/day 5 days out of 7. All dose modifications, interruptions or discontinuations must be based on the worst preceding toxicity as graded by the NCI Clinical Toxicity Criteria (NCI-CTCAE version 4.03. A change from continuous schedule to intermittent (5 days out of 7) must be preceded by 2 days without treatment.

Sponsors & Collaborators

  • Hospices Civils de Lyon

    lead OTHER

Principal Investigators

  • Françoise BORSON-CHAZOT, PUPH · Hospices Civils de Lyon

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-04-30
Primary Completion
2013-04-30
Completion
2017-01-31

Countries

  • France

Study Locations

More Related Trials

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01830504 on ClinicalTrials.gov