Identification of Molecular Biomarkers for Thyroid Cancer

• Conditions: Thyroid Cancer

• Registration Number: NCT04133870
• Lead Sponsor: Royal Marsden NHS Foundation Trust

Brief Summary

This is a two part study; part A proposes to collect plasma samples to examine how ctDNA (circulating thyroid DNA) markers correlate with detection of recurrent disease, response to therapy, clinical outcome and pathological data. Part B aims to use tissue obtained from biopsies of primary or recurrent disease to establish cell lines and tumour explants to further investigate the biology of thyroid cancer in the preclinical setting

Detailed Description

To collect blood and tumour tissue for Part A: molecular profiling, including extraction of DNA for sequencing, RNA for expression levels and to identify expressed fusion genes, and proteins for proteomic studies and Part B: for establishment of cell lines and patient derived xenograft (PDX) models of thyroid cancer.

1. To correlate BRAF V600E, RAS, RET/PTC, RET, PAX8/PPARϒ, βcatenin, p53, PTEN and PI3K mutations in ctDNA with Formalin Fixed Paraffin Embedded tumour tissue (FFPE) mutational analysis.

2. To correlate the quantity of ctDNA fragments 3 monthly in patients with advanced disease on routine follow up with conventional tumour markers (Tg, calcitonin, CEA).

3. To correlate the quantity of ctDNA fragments 3 monthly once relapse suspected by conventional methods (Tg, Calcitonin, CEA, radiological)

4. To correlate the quantity of ctDNA fragments with response (RECIST, Tg, Calcitonin and CEA) to targeted therapies

5. To assess prognostic significance of ctDNA levels in metastatic/advanced thyroid cancer

6. To isolate live tumor cells for studies of novel treatment strategies (combinatorial treatments), therapy resistance and thyroid cancer biology

7. Retrieval and analysis of archival primary tissue blocks for comparison with metastatic tumour sites

8. To collect blood for analysis of noninvasive tests of tumour phenotype

Study Timeline

• Study Start: 2015-12-21
• Study First Submitted: 2017-01-26
• Primary Completion: 2018-04-30
• Status Verified: 2018-11
• Study First Submitted QC: 2019-10-17
• Last Update Submitted: 2019-10-17
• Study First Posted: 2019-10-21
• Last Update Posted: 2019-10-21
• Study Completion: 2020-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• T3-4, N0-1b, M0-M1 thyroid cancer (papillary, follicular, poorly differentiated, anaplastic and medullary thyroid carcinoma).
• Patient able to provide informed consent
• Patient attending the Royal Marsden Hospital for inpatient or outpatient review
• Sufficient tissue sample available to perform analysis (archived or fresh)
• Adults >16 years old

Exclusion Criteria

• Patients unable to provide informed consent
• Thyroid lymphoma
• Metastases to the thyroid
• No histological confirmed diagnosis
• Only cytology available

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Objective	3 years (at end of study)	Part B: blood and tumour tissue will be assessed to establish cell lines and to determine patient derived xenograft (PDX) models of thyroid cancer

Trial Locations

Locations (1)

Royal Marsden NHS Foundation Trust; 🇬🇧 London, Sutton, United Kingdom