A Multicentre Prospective Study Investigating the Utility of ctDNA as a Biomarker of Disease Burden, Genetic Heterogeneity and Tumour Evolution in Advanced Thyroid Cancer

Study Overview
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Brief Summary
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Although most thyroid cancers are treated and cured successfully there are still 30% who recur after many years. This will eventually progress and at this point may become incurable with treatment options including complex and high risk surgery. The overall efficacy of systemic treatment in advanced thyroid cancer has a good initial response in most patients but not all. The treatment decisions are based on relying on radiological parameters such as using the RECIST criteria and measuring the rise in certain serum tumour biomarkers. However, the disadvantage of this is that this method can take many months to detect a change in disease volume. An improved understanding of genetics and cancer and potential gene sequencing can help achieve personalised treatment for patients. However, there are many questions and issues that still need to be answered and require urgent attention before being able to achieve optimate patient stratification. We need to identify better tumour biomarkers to detect disease progression, show real time response to treatment and understand why tumours evolve to becoming more aggressive. This study hopes to address these issues by proposing a multicentre prospective study to investigate the presence and role of ctDNA in advanced thyroid cancer including differentiated thyroid cancer , medullary thyroid cancer and Anaplastic Thyroid Cancer. The study will collect tissues and blood samples for various protein analysis, nucleic acid extraction and live cell analysis in order to try and detect the presence of plasma ctDNA at baseline of eligible patients.

Official Title
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A Multicentre Prospective Study Investigating the Utility of ctDNA as a Biomarker of Disease Burden, Genetic Heterogeneity and Tumour Evolution in Advanced Thyroid Cancer

Conditions
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Thyroid Cancer

Intervention / Treatment
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* Other: Sample collection only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I. Age 18 years or older. (all cohorts) II. Patients diagnosed with radioiodine refractory differentiated thyroid carcinoma (RR-DTC) under surveillance. (cohort 1) III. Patients with RR-DTC starting systemic therapy (cohort 3) IV. Patients with RR-DTC on systemic therapy (cohort 3) V. Patients with newly diagnosed resectable locally advanced medullary thyroid cancer (cohort 2) VI. Patients with newly diagnosed metastatic medullary thyroid cancer for surveillance (cohort 2) VII. Patients with locally advanced or metastatic medullary thyroid cancer on surveillance (cohort 2) VIII. Patients with MTC starting systemic therapy (cohort 3) IX. Patients with MTC on systemic therapy (cohort 3) X. Patients with newly diagnosed anaplastic thyroid cancer (cohort 4) XI. Availability of tissue from one archival diagnostic tumour tissue block or be willing to have biopsy of accessible disease (all cohorts) CONFIDENTIAL NOMINATE v1.6 13.12.2022 IRAS 310978 XII. Patients must be willing to undergo standard monitoring and treatment as recommended by their clinical team (all cohorts) XIII. Ability to give informed consent for biological sample collection. (all cohorts) Exclusion Criteria: I. Previous or concurrent illness, which in the investigator's opinion would interfere with collection of the complete sample collection II. Any invasive malignancy within previous 5 years (other than non melanomatous skin carcinoma or carcinoma in situ) III. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Patients with newly diagnosed iodine refractory thyroid cancer on surveillance | Other: Sample collection only<br>* Sample collection only<br>|
| Cohort 2<br>Patients with locally advanced and / or metastatic (Stage 3 & 4) medullary thyroid cancer | Other: Sample collection only<br>* Sample collection only<br>|
| Cohort 3<br>Patients with iodine refractory thyroid cancer or advanced/metastatic unresectable MTC due to commence systemic treatment or already on systemic treatment | Other: Sample collection only<br>* Sample collection only<br>|
| Cohort 4<br>Patients with newly diagnosed anaplastic thyroid cancer | Other: Sample collection only<br>* Sample collection only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of the proposed study is to determine the sensitivity of detecting the presence of plasma ctDNA in patients with advanced and recurrent thyroid cancer | The primary objective of the proposed study is to determine the sensitivity of detecting the presence of plasma ctDNA in patients with advanced and recurrent thyroid cancer | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of the absence of plasma ctDNA in patients with advanced and recurrent thyroid cancer at baseline | Specificity of the absence of plasma ctDNA in patients with advanced and recurrent thyroid cancer at baseline | 5 years | 
| Association of ctDNA levels as biomarker of disease burden compared with standard biochemical markers and radiological response | Association of ctDNA levels as biomarker of disease burden compared with standard biochemical markers and radiological response | 5 years | 
| Changes in ctDNA levels as biomarker of disease burden compared with standard biochemical markers and radiological response | Changes in ctDNA levels as biomarker of disease burden compared with standard biochemical markers and radiological response | 5 years | 
| ctDNA as a biomarker of response to systemic therapy (levels and timing) compared with standard biochemical markers and radiological response in patients starting/during systemic therapy | ctDNA as a biomarker of response to systemic therapy (levels and timing) compared with standard biochemical markers and radiological response in patients starting/during systemic therapy | 5 years | 
| ctDNA as a biomarker of progression free and overall survival | ctDNA as a biomarker of progression free and overall survival | 5 years |