Differentiated Thyroid CancerNCT01700699
Impact of BRAFV600E Intratumor Heterogeneity in Thyroid Cancer Treated With Tyrosine Kinase Inhibitors
An observational study of Differentiated Thyroid Cancer, run by University of Salerno at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Differentiated Thyroid Cancer
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2012to Oct 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: primary care clinic
Who may be able to join
- 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
Who cannot join
- concurrent Hashimoto's thyroiditis
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Department of Medicine and Surgery, Univeristy of Salerno
Baronissi, Salerno, 84081
Mario Vitale, MD, +39 089672539, mavitale@unisa.it
Mario Vitale, MD
About this study
Official title: Impact of BRAFV600E Intratumor Heterogeneity on the Efficacy of Tyrosine Kinase Inhibitors in the Treatment of Radioiodine-resistant Thyroid Cancer
- 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.
- Conditions
- Differentiated Thyroid Cancer
- Keywords
- thyroid cancer, tyrosine kinase inhibitors, BRAF, Sorafenib, Pazopanib, Sunitinib, Cabozantinib
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of BRAFV600E alleles in tumor tissue before TKI treatment
Measured: within 1 month after the patient has entered the study
Secondary outcomes (1)
Percentage of BRAFV600E alleles in tumor tissue post-TKI treatment
Measured: within 30 days from the availability of the tissue sample
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2013 (estimated)
- Study completionOct 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Salerno
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mario Vitale, University of Salerno
- Investigators
- Mario Vitale, MD, Principal investigator, Univeristy of Salerno, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01700699
- Sponsor's protocol ID
- BRAF-TKI-DTC1
- Status last verified
- Oct 2012
- First submitted
- 22 Sep 2012
- Last updated
- 23 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Guerra A, Fugazzola L, Marotta V, Cirillo M, Rossi S, Cirello V, Forno I, Moccia T, Budillon A, Vitale M. A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome. J Clin Endocrinol Metab. 2012 Jul;97(7):2333-40. doi: 10.1210/jc.2011-3106. Epub 2012 Apr 16.
PubMed 22508706Guerra A, Sapio MR, Marotta V, Campanile E, Rossi S, Forno I, Fugazzola L, Budillon A, Moccia T, Fenzi G, Vitale M. The primary occurrence of BRAF(V600E) is a rare clonal event in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2012 Feb;97(2):517-24. doi: 10.1210/jc.2011-0618. Epub 2011 Dec 14.
PubMed 22170714Gupta-Abramson V, Troxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K, Mandel SJ, Flaherty KT, Loevner LA, O'Dwyer PJ, Brose MS. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008 Oct 10;26(29):4714-9. doi: 10.1200/JCO.2008.16.3279. Epub 2008 Jun 9.
PubMed 18541894Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, Liang J, Wakely PE Jr, Vasko VV, Saji M, Rittenberry J, Wei L, Arbogast D, Collamore M, Wright JJ, Grever M, Shah MH. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009 Apr 1;27(10):1675-84. doi: 10.1200/JCO.2008.18.2717. Epub 2009 Mar 2.
PubMed 19255327
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of BRAFV600E Intratumor Heterogeneity on the Efficacy of Tyrosine Kinase Inhibitors in the Treatment of Radioiodine-resistant Thyroid Cancer
- ClinicalTrials.gov ID
- NCT01700699
- Acronym / sponsor ID
- BRAF-TKI-DTC1
- Conditions
- Differentiated Thyroid Cancer
- Keywords
- thyroid cancer, tyrosine kinase inhibitors, BRAF, Sorafenib, Pazopanib, Sunitinib, Cabozantinib
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of SalernoUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Oct 2013 (estimated)
- Study completion
- Oct 2013 (estimated)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- primary care clinic
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (1 listed)
- concurrent Hashimoto's thyroiditis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Percentage of BRAFV600E alleles in tumor tissue before TKI treatment
Time frame: within 1 month after the patient has entered the study
1 secondary outcome
Percentage of BRAFV600E alleles in tumor tissue post-TKI treatment
Time frame: within 30 days from the availability of the tissue sample
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2012.
- Background: PubMed 22508706Guerra A, Fugazzola L, Marotta V, Cirillo M, Rossi S, Cirello V, Forno I, Moccia T, Budillon A, Vitale M. A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome. J Clin Endocrinol Metab. 2012 Jul;97(7):2333-40. doi: 10.1210/jc.2011-3106. Epub 2012 Apr 16.
- Background: PubMed 22170714Guerra A, Sapio MR, Marotta V, Campanile E, Rossi S, Forno I, Fugazzola L, Budillon A, Moccia T, Fenzi G, Vitale M. The primary occurrence of BRAF(V600E) is a rare clonal event in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2012 Feb;97(2):517-24. doi: 10.1210/jc.2011-0618. Epub 2011 Dec 14.
- Background: PubMed 18541894Gupta-Abramson V, Troxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K, Mandel SJ, Flaherty KT, Loevner LA, O'Dwyer PJ, Brose MS. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008 Oct 10;26(29):4714-9. doi: 10.1200/JCO.2008.16.3279. Epub 2008 Jun 9.
- Background: PubMed 19255327Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, Liang J, Wakely PE Jr, Vasko VV, Saji M, Rittenberry J, Wei L, Arbogast D, Collamore M, Wright JJ, Grever M, Shah MH. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009 Apr 1;27(10):1675-84. doi: 10.1200/JCO.2008.18.2717. Epub 2009 Mar 2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Vitale, MD principal investigator
Univeristy of Salerno, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Differentiated Thyroid Cancer, run by University of Salerno at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mario Vitale, MD (+39 089672539, mavitale@unisa.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of BRAFV600E alleles in tumor tissue before TKI treatment (time frame: within 1 month after the patient has entered the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01700699, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2012.