Impact of BRAFV600E Intratumor Heterogeneity in Thyroid Cancer Treated With Tyrosine Kinase Inhibitors
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|ClinicalTrials.gov Identifier: NCT01700699|
Recruitment Status : Unknown
Verified October 2012 by Mario Vitale, University of Salerno.
Recruitment status was: Recruiting
First Posted : October 4, 2012
Last Update Posted : October 23, 2012
- Background: BRAFV600E is the most frequent oncogene in differentiated thyroid cancer (DTC) occurring in about 50% of cases. Clinical trials with tyrosine kinase inhibitors (TKI) with specific activity against BRAF in metastatic radioiodine-resistant DTC (MRR-DTC) are ongoing. Very recently it has been demonstrated that DTC often consists of a mixture of tumor cells with wild-type and mutant BRAF. The subclonal occurrence of BRAFV600E in MRR-DTC could disable the therapy with BRAF targeted TKI and be responsible of the frequent defeats of this treatment. A therapeutic strategy based upon BRAF inhibitors in tumors bearing subclonal BRAFV600E could be initially successful hitting the tumor cells expressing the oncogene, and after the initial tumor growth arrest and/or shrinkage, the oncogene negative cells insensitive or less sensitive to the treatment, could restart the growth of the tumor causing the progression of the disease and the escape from the clinical response.
- Aims: To determine the impact of subclonal BRAFV600E on the efficacy of BRAF inhibitors in the treatment of MRR-DTC.
- Study design: Primary tumor tissues will be analyzed for the presence of BRAFV600E by pyrosequencing or other quantitative assay. If available, synchronous metastases and post-therapy metachronous metastases will be analyzed as well. The clinical response will be determined according to RECIST, and the association with the percentage of BRAFV600E alleles will be evaluated. Attention will be paid to the possible difference of BRAFwild-type/BRAFV600E ratio between primary tumors and synchronous metastases, primary tumors and post-therapy metachronous metastases, and between responsive and resistant synchronous tumor lesions.
|Condition or disease|
|Differentiated Thyroid Cancer|
|Study Type :||Observational|
|Estimated Enrollment :||50 participants|
|Official Title:||Impact of BRAFV600E Intratumor Heterogeneity on the Efficacy of Tyrosine Kinase Inhibitors in the Treatment of Radioiodine-resistant Thyroid Cancer|
|Study Start Date :||October 2012|
|Estimated Primary Completion Date :||October 2013|
|Estimated Study Completion Date :||October 2013|
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Sorafenib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Axitinib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Pazopanib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with different type of tyrosine kinase inhibitor
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Motesanib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Sunitinib
- Percentage of BRAFV600E alleles in tumor tissue before TKI treatment [ Time Frame: within 1 month after the patient has entered the study ]
- Percentage of BRAFV600E alleles in tumor tissue post-TKI treatment [ Time Frame: within 30 days from the availability of the tissue sample ]
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01700699
|Contact: Mario Vitale, MD||+39 firstname.lastname@example.org|
|Department of Medicine and Surgery, Univeristy of Salerno||Recruiting|
|Baronissi, Salerno, Italy, 84081|
|Contact: Mario Vitale, MD +39 089672539 email@example.com|
|Principal Investigator: Mario Vitale, MD|
|Principal Investigator:||Mario Vitale, MD||Univeristy of Salerno, Italy|