ThyroidNCT02681328
Randomized Trial Comparing Performance of Molecular Markers for Indeterminate Thyroid Nodules
An observational study of Thyroid, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to compare the performance of Afirma GSC and ThyroSeq v.3 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Thyroid
- What is being tested?
- Afirma GEC, ThyroSeq v.2 and Afirma GSC
- How many people
- 328 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2016to 1 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients undergoing thyroid fine needle aspiration (FNA) within the University of California, Los Angeles (UCLA) Health System
Who may be able to join
- Patients with a thyroid nodule who have a thyroid biopsy performed at UCLA health will be eligible for the study and consented if they agree to participate.
- Patients who have an indeterminate FNA biopsy result (Bethesda category 3 or 4) will be enrolled in the study if they agree to participate.
Who cannot join
- Patients who do not have an indeterminate biopsy result (either patients who have a benign, insufficient, or malignant result).
Trial locations and contacts
1 site in 1 country.
United States1 site
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095-1781
About this study
The purpose of this study is to compare the performance of Afirma GSC and ThyroSeq v.3 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. In the initial phase of this study, the performance of Afirma GEC and ThyroSeq v.2 were compared.
Read the detailed description
- All patients undergoing thyroid FNA within the UCLA Health System will be randomized at the time of FNA to a single molecular test (GSC or ThyroSeq v.3). In the previous phase of the study, patients were randomized to the previous versions of a single molecular test (GEC or ThyroSeq v.2).
- During the FNA, a sample will be collected for the molecular test.
- If the cytology results are indeterminate (Bethesda categories 3 or 4), the molecular test will be reflexively sent off.
- We will help patients with indeterminate thyroid nodules to establish care with an endocrinologist, if they do not already have one. The physicians will make treatment recommendations using best practices and incorporating the results of the molecular test. We anticipate that most patients with a positive molecular test will undergo surgery, while the majority with a negative test will be surveiled.
- Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
- Patients who do not undergo surgery will have a followup ultrasound at 6 and 12 months, or sooner at the discretion of the treating physician.
- We will assess thyroid-specific quality of life at baseline (following initial diagnosis of an indeterminate thyroid nodule) and during followup (at 6 and 12 months) using the short version of Thyroid-Related Patient-Reported Outcome.
- Conditions
- Thyroid
- Being tested
- Afirma GEC, ThyroSeq v.2, Afirma GSC, ThyroSeq v.3
- Medical subject headings
- Thyroid Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Afirma GECOther
Afirma GEC molecular test on collected thyroid tissue
ThyroSeq v.2Other
ThyroSeq v.2 molecular test on collected thyroid tissue
Afirma GSCOther
Afirma GSC molecular test on collected thyroid tissue
ThyroSeq v.3Other
ThyroSeq v.3 molecular test on collected thyroid tissue
| Study group | Role | What they receive |
|---|---|---|
| Afirma GEC | single molecular test GEC of collected tissue Receives: Other: Afirma GEC | |
| ThyroSeq v.2 | single molecular test ThyroSeq v.2 of collected tissue Receives: Other: ThyroSeq v.2 | |
| Afirma GSC | single molecular test GSC of collected tissue Receives: Other: Afirma GSC | |
| ThyroSeq v.3 | single molecular test ThyroSeq v.3 of collected tissue Receives: Other: ThyroSeq v.3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Afirma GEC vs. ThyroSeq v.2 in indeterminate thyroid nodules post best practices surgery
compare the performance of Afirma GEC and ThyroSeq v.2 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. (5) Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
Measured: 12 months. [This phase of the study is now completed]
2. Afirma GSC vs. ThyroSeq v.3 in indeterminate thyroid nodules post best practices surgery
compare the performance of Afirma GSC and ThyroSeq v.3 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. (5) Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
Measured: 12 months.
Secondary outcomes (1)
Avoidance of unnecessary surgeries
Determine the number of unnecessary surgeries avoided based on the number of false-positive test results, and assess whether this translated into improved quality of life.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2016 (estimated)
- Study start1 May 2016
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for ThyroidStudies 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
- Prospective
- Enrolment
- 328 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Masha Livhits, MC, Principal investigator, Visiting Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02681328
- Sponsor's protocol ID
- 16-000055
- Status last verified
- Dec 2025
- First submitted
- 10 Feb 2016
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009 Nov;132(5):658-65. doi: 10.1309/AJCPPHLWMI3JV4LA.
PubMed 19846805Lee L, How J, Tabah RJ, Mitmaker EJ. Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology. J Clin Endocrinol Metab. 2014 Aug;99(8):2674-82. doi: 10.1210/jc.2014-1219. Epub 2014 Mar 31.
PubMed 24684467Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012 Aug 23;367(8):705-15. doi: 10.1056/NEJMoa1203208. Epub 2012 Jun 25.
PubMed 22731672Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, Gooding WE, LeBeau SO, Ohori NP, Seethala RR, Tublin ME, Yip L, Nikiforova MN. Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology. Thyroid. 2015 Nov;25(11):1217-23. doi: 10.1089/thy.2015.0305. Epub 2015 Sep 10.
PubMed 26356635Wu JX, Lam R, Levin M, Rao J, Sullivan PS, Yeh MW. Effect of malignancy rates on cost-effectiveness of routine gene expression classifier testing for indeterminate thyroid nodules. Surgery. 2016 Jan;159(1):118-26. doi: 10.1016/j.surg.2015.05.035. Epub 2015 Oct 2.
PubMed 26435428Wu JX, Young S, Hung ML, Li N, Yang SE, Cheung DS, Yeh MW, Livhits MJ. Clinical Factors Influencing the Performance of Gene Expression Classifier Testing in Indeterminate Thyroid Nodules. Thyroid. 2016 Jul;26(7):916-22. doi: 10.1089/thy.2015.0505. Epub 2016 Jun 9.
PubMed 27161519Hu TX, Nguyen DT, Patel M, Beckett K, Douek M, Masamed R, Rhyu J, Kim J, Tseng CH, Yeh MW, Livhits MJ. The Effect Modification of Ultrasound Risk Classification on Molecular Testing in Predicting the Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules. Thyroid. 2022 Aug;32(8):905-916. doi: 10.1089/thy.2021.0659. Epub 2022 Jun 23.
PubMed 35611970Zhu CY, Donangelo I, Gupta D, Nguyen DT, Ochoa JE, Yeh MW, Livhits MJ. Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing. J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1240-e1247. doi: 10.1210/clinem/dgaa887.
PubMed 33394039Livhits MJ, Zhu CY, Kuo EJ, Nguyen DT, Kim J, Tseng CH, Leung AM, Rao J, Levin M, Douek ML, Beckett KR, Cheung DS, Gofnung YA, Smooke-Praw S, Yeh MW. Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules: A Randomized Clinical Trial. JAMA Oncol. 2021 Jan 1;7(1):70-77. doi: 10.1001/jamaoncol.2020.5935.
PubMed 33300952Livhits MJ, Kuo EJ, Leung AM, Rao J, Levin M, Douek ML, Beckett KR, Zanocco KA, Cheung DS, Gofnung YA, Smooke-Praw S, Yeh MW. Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2261-2268. doi: 10.1210/jc.2017-02754.
PubMed 29590358
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial Comparing Performance of Molecular Markers for Indeterminate Thyroid Nodules
- ClinicalTrials.gov ID
- NCT02681328
- Acronym / sponsor ID
- 16-000055
- Conditions
- Thyroid
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 328 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 May 2016 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 12 Feb 2016 (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.
The purpose of this study is to compare the performance of Afirma GSC and ThyroSeq v.3 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. In the initial phase of this study, the performance of Afirma GEC and ThyroSeq v.2 were compared.
Detailed description
- All patients undergoing thyroid FNA within the UCLA Health System will be randomized at the time of FNA to a single molecular test (GSC or ThyroSeq v.3). In the previous phase of the study, patients were randomized to the previous versions of a single molecular test (GEC or ThyroSeq v.2).
- During the FNA, a sample will be collected for the molecular test.
- If the cytology results are indeterminate (Bethesda categories 3 or 4), the molecular test will be reflexively sent off.
- We will help patients with indeterminate thyroid nodules to establish care with an endocrinologist, if they do not already have one. The physicians will make treatment recommendations using best practices and incorporating the results of the molecular test. We anticipate that most patients with a positive molecular test will undergo surgery, while the majority with a negative test will be surveiled.
- Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
- Patients who do not undergo surgery will have a followup ultrasound at 6 and 12 months, or sooner at the discretion of the treating physician.
- We will assess thyroid-specific quality of life at baseline (following initial diagnosis of an indeterminate thyroid nodule) and during followup (at 6 and 12 months) using the short version of Thyroid-Related Patient-Reported Outcome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Afirma GEC | – | Other: Afirma GECsingle molecular test GEC of collected tissue |
| ThyroSeq v.2 | – | Other: ThyroSeq v.2single molecular test ThyroSeq v.2 of collected tissue |
| Afirma GSC | – | Other: Afirma GSCsingle molecular test GSC of collected tissue |
| ThyroSeq v.3 | – | Other: ThyroSeq v.3single molecular test ThyroSeq v.3 of collected tissue |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing thyroid fine needle aspiration (FNA) within the University of California, Los Angeles (UCLA) Health System
Key inclusion criteria (2 listed)
- Patients with a thyroid nodule who have a thyroid biopsy performed at UCLA health will be eligible for the study and consented if they agree to participate.
- Patients who have an indeterminate FNA biopsy result (Bethesda category 3 or 4) will be enrolled in the study if they agree to participate.
Key exclusion criteria (1 listed)
- Patients who do not have an indeterminate biopsy result (either patients who have a benign, insufficient, or malignant result).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Afirma GECAfirma GEC molecular test on collected thyroid tissue | Other | Afirma GEC |
| ThyroSeq v.2ThyroSeq v.2 molecular test on collected thyroid tissue | Other | ThyroSeq v.2 |
| Afirma GSCAfirma GSC molecular test on collected thyroid tissue | Other | Afirma GSC |
| ThyroSeq v.3ThyroSeq v.3 molecular test on collected thyroid tissue | Other | ThyroSeq v.3 |
Primary outcome
Afirma GEC vs. ThyroSeq v.2 in indeterminate thyroid nodules post best practices surgery
Time frame: 12 months. [This phase of the study is now completed]
compare the performance of Afirma GEC and ThyroSeq v.2 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. (5) Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
2. Afirma GSC vs. ThyroSeq v.3 in indeterminate thyroid nodules post best practices surgery
Time frame: 12 months.
compare the performance of Afirma GSC and ThyroSeq v.3 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. (5) Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
1 secondary outcome
Avoidance of unnecessary surgeries
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Background: PubMed 19846805Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009 Nov;132(5):658-65. doi: 10.1309/AJCPPHLWMI3JV4LA.
- Background: PubMed 24684467Lee L, How J, Tabah RJ, Mitmaker EJ. Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology. J Clin Endocrinol Metab. 2014 Aug;99(8):2674-82. doi: 10.1210/jc.2014-1219. Epub 2014 Mar 31.
- Background: PubMed 22731672Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012 Aug 23;367(8):705-15. doi: 10.1056/NEJMoa1203208. Epub 2012 Jun 25.
- Background: PubMed 26356635Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, Gooding WE, LeBeau SO, Ohori NP, Seethala RR, Tublin ME, Yip L, Nikiforova MN. Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology. Thyroid. 2015 Nov;25(11):1217-23. doi: 10.1089/thy.2015.0305. Epub 2015 Sep 10.
- Background: PubMed 26435428Wu JX, Lam R, Levin M, Rao J, Sullivan PS, Yeh MW. Effect of malignancy rates on cost-effectiveness of routine gene expression classifier testing for indeterminate thyroid nodules. Surgery. 2016 Jan;159(1):118-26. doi: 10.1016/j.surg.2015.05.035. Epub 2015 Oct 2.
- Background: PubMed 27161519Wu JX, Young S, Hung ML, Li N, Yang SE, Cheung DS, Yeh MW, Livhits MJ. Clinical Factors Influencing the Performance of Gene Expression Classifier Testing in Indeterminate Thyroid Nodules. Thyroid. 2016 Jul;26(7):916-22. doi: 10.1089/thy.2015.0505. Epub 2016 Jun 9.
- Derived from this study: PubMed 35611970Hu TX, Nguyen DT, Patel M, Beckett K, Douek M, Masamed R, Rhyu J, Kim J, Tseng CH, Yeh MW, Livhits MJ. The Effect Modification of Ultrasound Risk Classification on Molecular Testing in Predicting the Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules. Thyroid. 2022 Aug;32(8):905-916. doi: 10.1089/thy.2021.0659. Epub 2022 Jun 23.
- Derived from this study: PubMed 33394039Zhu CY, Donangelo I, Gupta D, Nguyen DT, Ochoa JE, Yeh MW, Livhits MJ. Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing. J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1240-e1247. doi: 10.1210/clinem/dgaa887.
- Derived from this study: PubMed 33300952Livhits MJ, Zhu CY, Kuo EJ, Nguyen DT, Kim J, Tseng CH, Leung AM, Rao J, Levin M, Douek ML, Beckett KR, Cheung DS, Gofnung YA, Smooke-Praw S, Yeh MW. Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules: A Randomized Clinical Trial. JAMA Oncol. 2021 Jan 1;7(1):70-77. doi: 10.1001/jamaoncol.2020.5935.
- Derived from this study: PubMed 29590358Livhits MJ, Kuo EJ, Leung AM, Rao J, Levin M, Douek ML, Beckett KR, Zanocco KA, Cheung DS, Gofnung YA, Smooke-Praw S, Yeh MW. Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2261-2268. doi: 10.1210/jc.2017-02754.
- Individual participant dataSharing planned: No
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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.
Masha Livhits, MC principal investigator
Visiting Assistant Professor
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 Thyroid, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
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 2 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: under way, not looking for participants, as of the sponsor's last update on 22 Dec 2025. 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Afirma GEC vs. ThyroSeq v.2 in indeterminate thyroid nodules post best practices surgery (time frame: 12 months. [This phase of the study is now completed]). The study lists 2 primary outcomes in all. 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 NCT02681328, which also lists 10 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 22 Dec 2025.