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Impact of BRAFV600E Intratumor Heterogeneity in Thyroid Cancer Treated With Tyrosine Kinase Inhibitors

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2012 by Mario Vitale, University of Salerno.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01700699
First Posted: October 4, 2012
Last Update Posted: October 23, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Mario Vitale, University of Salerno
  Purpose
  • 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
Differentiated Thyroid Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Impact of BRAFV600E Intratumor Heterogeneity on the Efficacy of Tyrosine Kinase Inhibitors in the Treatment of Radioiodine-resistant Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by Mario Vitale, University of Salerno:

Primary Outcome Measures:
  • Percentage of BRAFV600E alleles in tumor tissue before TKI treatment [ Time Frame: within 1 month after the patient has entered the study ]

Secondary Outcome Measures:
  • 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
Primary and metastatic tumor tissue, frozen or formaldehyde fixed-paraffin embedded from block, genomic DNA already extracted from tumor tissue

Estimated Enrollment: 50
Study Start Date: October 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Sorafenib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Sorafenib
Axitinib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Axitinib
Pazopanib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Pazopanib
TKI
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with different type of tyrosine kinase inhibitor
Motesanib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Motesanib
Sunitinib
Assessment of percentage of BRAFV600E in tissue specimens of MRR-DTC patients treated with Sunitinib

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
primary care clinic
Criteria

Inclusion Criteria:

  • subjects any sex any age with metastatic or unresectable thyroid carcinoma treated with tyrosine kinase inhibitors
  • evidence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)
  • availability of study end points including best response, duration of response, and time to disease progression (based on RECIST), clinical progression, or death
  • availability of tumor tissue samples, frozen or formaldehyde fixed-paraffin embedded from block, genomic DNA already extracted from tumor tissue

Exclusion Criteria:

  • concurrent Hashimoto's thyroiditis
  Contacts and Locations
Information from the National Library of Medicine

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): NCT01700699


Contacts
Contact: Mario Vitale, MD +39 089672539 mavitale@unisa.it

Locations
Italy
Department of Medicine and Surgery, Univeristy of Salerno Recruiting
Baronissi, Salerno, Italy, 84081
Contact: Mario Vitale, MD    +39 089672539    mavitale@unisa.it   
Principal Investigator: Mario Vitale, MD         
Sponsors and Collaborators
University of Salerno
Investigators
Principal Investigator: Mario Vitale, MD Univeristy of Salerno, Italy
  More Information

Publications:
Responsible Party: Mario Vitale, Professor of Endocrinology at the School of Medicine, University of Salerno, Director of the Endocrinology Unit, University Hospital of Salerno, Italy, University of Salerno
ClinicalTrials.gov Identifier: NCT01700699     History of Changes
Other Study ID Numbers: BRAF-TKI-DTC1
First Submitted: September 22, 2012
First Posted: October 4, 2012
Last Update Posted: October 23, 2012
Last Verified: October 2012

Keywords provided by Mario Vitale, University of Salerno:
thyroid cancer
tyrosine kinase inhibitors
BRAF
Sorafenib
Pazopanib
Sunitinib
Cabozantinib

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Sorafenib
Sunitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors