Molecular Analysis for Thyroid Cancer

(MAPS Trial)

Overseen By Elena G Hughes

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Disqualifiers: Prior thyroid operation, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best surgical option for patients with certain types of thyroid cancer. Researchers aim to determine if molecular analysis (a detailed examination of the tumor's DNA) before surgery can guide the decision between removing part of the thyroid or the entire gland. Participants with intermediate-risk cancer will be randomly assigned to either surgery type. This study is suitable for English-speaking adults with specific thyroid nodules confirmed by biopsy and no prior thyroid surgery.

As an unphased trial, it offers participants the chance to contribute to innovative research that may enhance surgical decision-making for future patients.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that molecular analysis for thyroid resection is safe?

Research shows that molecular analysis during thyroid cancer surgery helps doctors determine how much of the thyroid to remove. This approach is safe, as it enhances understanding of the cancer before surgery without introducing new drugs or treatments.

Studies have found that molecular tests can predict thyroid cancer behavior. These highly sensitive tests detect even small changes in cancer cells, helping to avoid unnecessary surgeries. The molecular analysis itself has no specific side effects, as it serves only to gather information, not as a treatment.

Overall, molecular analysis in thyroid cancer surgery is well-tolerated, aiding informed decisions without adding new risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the effectiveness of two surgical approaches for thyroid cancer, which could optimize treatment decisions for patients. Unlike the standard approach that often relies on a total thyroidectomy, this trial investigates whether a thyroid lobectomy, where only part of the thyroid is removed, can be just as effective for patients with intermediate molecular-risk nodules. By comparing these two methods, the trial aims to determine if a less extensive surgery can offer similar outcomes, potentially leading to fewer complications and better quality of life for patients.

What evidence suggests that this trial's treatments could be effective for thyroid cancer?

This trial will compare two surgical approaches for patients with intermediate molecular-risk thyroid nodules: thyroid lobectomy and total thyroidectomy. Studies have shown that molecular testing can help doctors select the best surgical option for thyroid cancer. This testing examines genetic changes in thyroid nodules to predict their cancerous potential. Research indicates that this analysis improves prediction accuracy, aiding doctors in deciding whether to remove part or all of the thyroid gland. In some studies, this testing led to better surgical decisions and increased the chances of a successful outcome. By understanding the genetic details of the nodules, doctors can tailor the surgery to the patient's specific needs. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with a confirmed diagnosis of papillary thyroid cancer or other thyroid diseases, specifically those classified as Bethesda V and VI. Participants must be willing to undergo preoperative molecular analysis to guide the surgical approach: partial or complete removal of the thyroid.

Inclusion Criteria

English-speaking

My thyroid nodule is classified as high risk and is between 1-4cm.

My thyroid nodule is Bethesda III or IV with intermediate risk.

Exclusion Criteria

I have had surgery on my thyroid.

My cancer has spread to distant parts of my body.

My thyroid cancer has spread beyond the thyroid or to lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Molecular Testing

Participants undergo Thyroseq molecular testing to stratify thyroid cancer risk

4 weeks

1 visit (in-person)

Randomization and Treatment

Intermediate-risk patients are randomized to thyroid lobectomy or total thyroidectomy

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Routine follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Molecular Analysis for Thyroid Resection

Trial Overview The study is testing whether routine molecular analysis before surgery can help decide if patients should have part (thyroid lobectomy) or all (total thyroidectomy) of their thyroid removed. It's a pilot study that randomly assigns some patients to either surgery based on their molecular risk level.

How Is the Trial Designed?

Group I: Thyroid Lobectomy Active Control 1 Intervention

Randomization Protocol Patients with intermediate molecular-risk thyroid nodules will be randomized to thyroid lobectomy or total thyroidectomy. We will perform a 1:1 randomization in a consecutive manner. Patients will be informed of what operation they will receive and providers will also be aware what operation was performed as it dictates care moving forward. Details of operative management will be discussed further. Peri-operative Protocol Thyroid Lobectomy Patients undergoing thyroid lobectomy will have the thyroid lobe containing the cancer removed in the standard surgical technique. These operations will be performed at either the UCLA Health Westwood Ambulatory Surgery Center, UCLA Ronald Reagan Medical Center, or UCLA Santa Monica Medical Center. Patients will undergo our usual postoperative care.

Group II: Total Thyroidectomy Active Control 1 Intervention

Randomization Protocol Patients with intermediate molecular-risk thyroid nodules will be randomized to thyroid lobectomy or total thyroidectomy. We will perform a 1:1 randomization in a consecutive manner. Patients will be informed of what operation they will receive and providers will also be aware what operation was performed as it dictates care moving forward. Details of operative management will be discussed further. Total Thyroidectomy and Completion Thyroidectomy Patients undergoing total thyroidectomy will have their whole thyroid gland removed in the standard surgical technique. Patients undergoing a completion thyroidectomy will have their remaining thyroid lobe removed. These operations will be performed at UCLA Ronald Reagan Medical Center or UCLA Santa Monica Medical Center. Patients will undergo our usual postoperative care.

Molecular Analysis for Thyroid Resection is already approved in United States, European Union for the following indications:

Approved in United States as Molecular Analysis for Thyroid Resection for:

• Differentiated thyroid cancer

Approved in European Union as Molecular Analysis for Thyroid Resection for:

• Thyroid cancer diagnosis and surgical planning

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

In a study of 103 patients with malignant thyroid tumors, specific mutations like BRAF V600E, RET/PTC1 rearrangement, and TERT promoter mutations were linked to more aggressive tumor behavior, including extra-thyroidal extension and lymph node metastasis.

Molecular testing for these mutations can help predict the aggressiveness of thyroid cancers, which may guide surgical decisions and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mutations as a possible factor for determining extent of thyroid surgery. Krasner, JR., Alyouha, N., Pusztaszeri, M., et al.[2020]

Molecular profiling tests for thyroid nodules are becoming essential tools for surgeons, particularly in making decisions about surgery and the extent of resection, especially for cases with indeterminate fine-needle aspiration cytology.

The effectiveness of these diagnostic tests is highly dependent on the prevalence of cancer in specific cytologic categories at individual medical centers, highlighting the importance of understanding local cancer rates to accurately interpret test results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making. Ferris, RL., Baloch, Z., Bernet, V., et al.[2023]

Molecular testing can enhance the assessment of malignancy risk in indeterminate thyroid nodules, potentially guiding better surgical decisions, although its impact on modifying surgery extent remains uncertain.

Integrating molecular characterization into clinical management for advanced thyroid cancers can help identify actionable mutations and improve treatment outcomes while minimizing toxicity, especially with the availability of selective kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer. Valderrabano, P., Eszlinger, M., Stewardson, P., et al.[2023]

In a study of 578 thyroid cancer patients, molecular testing categorized tumors into three risk groups, revealing that higher risk groups were associated with more aggressive tumor characteristics and a higher likelihood of recurrence.

Patients with molecular risk group-high cancers had a significantly increased risk of recurrence compared to those in the intermediate and low groups, with hazard ratios indicating a fourfold and fivefold increase in recurrence risk, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of comprehensive thyroid cancer molecular profiling with tumor phenotype and cancer-specific outcomes. Liu, JB., Ramonell, KM., Carty, SE., et al.[2022]

Molecular testing for mutations like BRAF, RAS, and RET/PTC in thyroid cancer can help accurately diagnose and manage differentiated thyroid cancer, potentially reducing unnecessary surgeries by identifying benign cases.

About 20% to 30% of certain thyroid lesions are malignant, while 70% to 80% of diagnostic thyroid surgeries reveal benign conditions, highlighting the importance of molecular testing to improve patient outcomes and tailor treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and management of differentiated thyroid cancer using molecular biology. Witt, RL., Ferris, RL., Pribitkin, EA., et al.[2022]

Molecular genetic analysis of thyroid nodules, particularly through fine-needle aspiration biopsy (FNAB), is becoming an important tool in diagnosing thyroid cancer and determining which patients may need surgery versus those who can be monitored safely.

Understanding the genetics of thyroid cancer can help in personalizing treatment plans and improving management strategies for patients, as it provides insights into prognosis and the likelihood of recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science. Richmond, BK., Gallimore, J.[2023]

Molecular testing for thyroid nodules with malignant cytology (Bethesda VI) shows a high BRAF mutation detection rate of 70%, indicating its potential value in risk assessment for elective surgeries during a pandemic.

Incorporating additional gene alterations and classifiers can significantly enhance diagnostic accuracy, raising the detection rate of actionable mutations to as high as 95%, which supports better surgical and therapeutic decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative molecular testing in thyroid nodules with Bethesda VI cytology: Clinical experience and review of the literature. Labourier, E., Fahey, TJ.[2021]

Molecular testing for thyroid cancer can effectively reclassify over 50% of patients with indeterminate thyroid nodules, helping to identify benign cases and potentially avoiding unnecessary surgeries.

Understanding the molecular risk profile of thyroid nodules, along with clinical and radiologic features, can guide better surgical decisions for patients with suspicious or positive malignancy results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada. Rajab, M., Payne, RJ., Forest, VI., et al.[2022]

A new molecular test analyzing the expression of 19 genes has been developed to help distinguish between malignant and benign thyroid tumors, validated in a study of 730 patients with thyroid nodules.

In a separate analysis of 200 papillary thyroid carcinomas, significant genetic differences were found, with over 75% of invasive tumors showing specific mutations, which could aid in identifying tumors with a higher risk of metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular analyses of thyroid tumors for diagnosis of malignancy on fine-needle aspiration biopsies and for prognosis of invasiveness on surgical specimens. Rousset, B., Ziercher, L., Borson-Chazot, F.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12383582/

Molecular Testing in Thyroid Nodules: How Much Does It ... The aim of this study is to identify clinical factors that influence the decision to proceed with surgery in the presence of a benign molecular ...

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2773499

Effectiveness of Molecular Testing Techniques for ... This randomized clinical trial compares the diagnostic performance between an RNA test and a DNA-RNA test in patients with thyroid nodules.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06235814

Molecular Analysis for Precision Surgery in Thyroid Cancer ... This is the most robust method to determine whether outcomes are similar between thyroid lobectomy and total thyroidectomy. Currently, no randomized trial data ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9999006/

Molecular diagnostics in the evaluation of thyroid nodules Over the last 15-20 years, rapid advances have been made in cytomolecular testing to aid in thyroid nodule management.

5. mdpi.com mdpi.com/2072-6694/17/7/1156

Impact of Molecular Testing on Surgical Decision-Making ... Molecular testing has emerged as a promising tool to improve decision-making by predicting whether a nodule is likely to be benign or malignant.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9454567/

Molecular Testing for Thyroid Nodules - PubMed Central - NIH The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4519104/

American Thyroid Association Statement on Surgical ... This review covers the clinical scenarios by cytologic category for which the thyroid surgeon may find molecular profiling results useful.

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/14/NCT06235814/Prot_SAP_001.pdf

Molecular Analysis for Precision Surgery in Thyroid Cancer ... Patients' thyroid cancer molecular profile will be classified as low, intermediate, or high molecular-risk based on previous published data.4 ...

9. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=39720

Molecular Testing for Risk Stratification of Thyroid Nodules These data demonstrated high sensitivity (97-100%) and reasonably high specificity (80-85%) for both tests and diagnostic surgery was avoided in approximately ...