A Multicenter Phase II Pilot Open Label (BKM120)
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|ClinicalTrials.gov Identifier: NCT01830504|
Recruitment Status : Unknown
Verified October 2016 by Hospices Civils de Lyon.
Recruitment status was: Active, not recruiting
First Posted : April 12, 2013
Last Update Posted : October 5, 2016
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
|Condition or disease||Intervention/treatment||Phase|
|Thyroid Cancers||Drug: BKM120||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||April 2013|
|Estimated Study Completion Date :||January 2017|
|Experimental: NVP-BKM120 (BKM120) PI3K inhibitor||
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.
- progression-free survival (PFS) [ Time Frame: at 6 months after the onset of the treatment ]The progression-free survival is defined as a lack of objective tumor progression and death. Tumor progression is documented by the CT or MRI scans. Progression is defined according to RECIST criteria (version 1.1.).
- progression-free survival (PFS) [ Time Frame: PFS at 12 months after the onset of the treatment ]
- Objective tumor response (CR and PR) [ Time Frame: at 6 months after the onset of the treatment ]according to RECIST criteria (version 1.1.) and validated by a central review committee.
- Overall survival [ Time Frame: at 6 months after the onset of the treatment ]Overall survival (defined as the time from start of study treatment to the date of death due to any cause)
- safety and tolerance of BKM120 of BKM120: monitoring and recording AE and SAE, monitoring of hematology, blood chemistry and urine values, vital signs, physical examinations, skin, cardiac assessments and mood evaluation. [ Time Frame: After the patient has provided informed consent and until 4 weeks after the patient has stopped study participation. Assessments are performed at least every month during the first year, every 3 month until 12 months and every 4 months after this period. ]
Safety and tolerability will be assessed according to the NIH/NCI CTC (V4.0). Care will be taken to the monitoring of haematology, kidney function, liver function, endocrin/metabolic function, cardiac function, mood and rash evaluation.
Blood chemistry and urine will be considered. The others assessment will be: physical examination, ECOG performance status, body weight, vital signs, PHQ9 and GAD7 questionnaires, ECG and CT or MRI scans.
For patients who do not tolerate the protocol-specified dosing schedule, dose modification and/or dose interruption are permitted.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01830504
|Hospices Civils de Lyon|
|Lyon, France, 69003|
|Study Director:||Françoise BORSON-CHAZOT, PUPH||Hospices Civils de Lyon|