Identification of Molecular Biomarkers for Thyroid Cancer

Exploratory Study of the Molecular Profile of Thyroid Cancer

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

Study Overview

• Status: Unknown
• Conditions: Thyroid Cancer

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 Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• United Kingdom
  • Sutton
    • London, Sutton, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This is a biological study to obtain tissue and blood samples from patients with advanced thyroid cancer

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective	Part A: blood and tumour tissue will be measured to determine molecular profiling.	3 Years (at the end of study)
Primary Objective	Part B: blood and tumour tissue will be assessed to establish cell lines and to determine patient derived xenograft (PDX) models of thyroid cancer	3 years (at end of study)

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): December 21, 2015
• Primary Completion (Actual): April 30, 2018
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: November 1, 2018

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: CCR4343

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