Investigating Utility of ctDNA and Tumour Evolution in Advanced Thyroid Cancer (NOMINATE)

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

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 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.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Cancer
• Intervention / Treatment: Other: Sample collection only

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Leslie Cheng; Phone Number: 02000000000; Email: leslie.cheng@rmh.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
    • Contact: Leslie Cheng; Email: leslie.cheng@rmh.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with thyroid cancer

Description

Inclusion Criteria:

• Age 18 years or older. (all cohorts)
• Patients diagnosed with radioiodine refractory differentiated thyroid carcinoma (RR-DTC) under surveillance. (cohort 1)
• Patients with newly diagnosed resectable locally advanced medullary thyroid cancer Or Patients with newly diagnosed metastatic medullary thyroid cancer for surveillance Or Patients with locally advanced or metastatic medullary thyroid cancer on surveillance (cohort 2)
• Patients with RR-DTC starting systemic therapy Or Patients with RR-DTC on systemic therapy Or Patients with MTC starting systemic therapy Or Patients with MTC on systemic therapy (cohort 3)
• Patients with newly diagnosed anaplastic thyroid cancer (cohort 4)
• Availability of tissue from one archival diagnostic tumour tissue block or be willing to have biopsy of accessible disease (all cohorts)
• Patients must be willing to undergo standard monitoring and treatment as recommended by their clinical team (all cohorts)
• Ability to give informed consent for biological sample collection. (all cohorts)

Exclusion Criteria:

• Previous or concurrent illness, which in the investigator's opinion would interfere with collection of the complete sample collection
• Any invasive malignancy within previous 5 years (other than non-melanomatous skin carcinoma or carcinoma in situ)
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Patients with newly diagnosed iodine refractory thyroid cancer on surveillance	Other: Sample collection only; Sample collection only
Cohort 2; Patients with locally advanced and / or metastatic (Stage 3 & 4) medullary thyroid cancer	Other: Sample collection only; Sample collection only
Cohort 3; 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; Sample collection only
Cohort 4; Patients with newly diagnosed anaplastic thyroid cancer	Other: Sample collection only; Sample collection only

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Investigators: Principal Investigator: Kate Newbold, Royal Marsden NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Estimated): February 7, 2027
• Study Completion (Estimated): February 7, 2027

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: April 28, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: CCR5637

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No