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Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3

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ClinicalTrials.gov Identifier: NCT03488134
Recruitment Status : Active, not recruiting
First Posted : April 4, 2018
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Tracking Information
First Submitted Date March 28, 2018
First Posted Date April 4, 2018
Last Update Posted Date November 5, 2020
Actual Study Start Date August 3, 2018
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 11, 2018)
Prognostic biological markers via this prospective study [ Time Frame: 3 years ]
The study was designed as prospective pattern, and the investigators enrolled thyroid cancer with follow-up, then urine exosome protein will be measured and reported. The investigators try to find the correlation of outcome ( including recurrence, lymph nodes metastasis..) together with unknown/fresh biomarkers in this study and time-dependent manner. Such biomarkers including thyroglobulin, galectin-3, Calprotectin A8, Calprotectin A9, TKT, Annexin II, Afamin, Keratin 8, Keratin 9, Angiopoietin-1 and TIMP will be measured.
Original Primary Outcome Measures
 (submitted: March 28, 2018)
Prognostic biological markers via this prospective study [ Time Frame: 3 years ]
The study was designed as prospective pattern, and the investigators enrolled thyroid cancer with follow-up, then detect urine exosome and proteins (thyroglobulin and galectin-3). The investigators try to find the correlation of outcome ( including recurrence, lymph nodes metastasis..) together with unknown/fresh biomarkers in this study and time-dependent manner.
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3
Official Title A Prospective Study of Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3
Brief Summary

Although thyroid cancers are low-grade endocrine malignancy, most patients usually received thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Prior researches indicated that one-third well-differentiated thyroid cancers could transform to poorly-differentiated patterns, even to be anaplastic thyroid cancer (ATC), a fatal malignancy, and no effective therapeutic strategies was noted, including surgical intervention, chemotherapy and radiotherapy. The poorly-differentiated or anaplastic change of thyroid cancer cells proliferates rapidly and always invades local tissues with distant metastasis. Cellular de-differentiation is the most pivotal cause for malignant transformation and invasion. De-differentiation usually in papillary thyroid cancer and follicular thyroid cancer, and definitely in ATC. Therefore, the investigators try to find the biological markers and therapeutic targets via the exosomal expression in urine. On the continuing basis of prior ATC cells culture experiments.

Exosomes are nanovesicles secreted into extracellular environments. Cancer cell-derived exosomes could be found in plasma, saliva, urine and other body fluid of patients with cancer. The investigators try to analyze the urinary exosomal proteins, including thyroglobulin and galectin-3, to find the early prognostic biological markers in urine via this prospective study.

The investigators expected to enroll 150 post-operative patients with papillary, follicular or anaplastic thyroid cancer, and collect the urine samples in outpatient clinic per year. The investigators will analyze the urine exosomal proteins and probable biological markers, including thyroglobulin and galectin-3. The investigators hope to find the prognostic biological markers via this prospective study. The investigators further hope to find newly therapeutic and follow-up pathway for such patients with well-differentiated or anaplastic thyroid cancer.

Detailed Description

Papillary and follicular thyroid cancers are low-grade endocrine malignancy, and most patients usually received thyroidectomy with ablative radioactive iodine therapy. These patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Serum thyroglobulin is the pivotal biomarker in survey of possible residual tumor or recurrence of thyroid cancer. Generally, such patients appear to have the higher residual risk of isolated thyroglobulinemia, and postoperative serum thyroglobulin may suggest distant metastases. Low-risk patients with a non-stimulated postoperative serum thyroglobulin was usually defined of less than 0.4 ng/mL or with thyroid hormone withdrawal thyroglobulin of less than 1.0 ng/mL. However, expensive recombinant human TSH (rhTSH) is usually needed to stimulate serum thyroglobulin for detecting local recurrence or distant metastasis. The issue of earlier biological markers for predicting prognosis of thyroid cancer should be raised.

Exosomes are nanovesicles secreted into extracellular environments. Cancer cell-derived exosomes could be found in plasma, saliva, urine and other body fluid of patients with cancer. A growing evidence suggests that exosomes could be used as biomarkers to be the diagnosis and prognosis of malignant tumors. Exosomes are 40-100 nm diameters, and correspond to the intraluminal vesicles of endosomal multivesicular bodies. Exosomes secreted by cells could micro-molecularly transfer messages between cells, and be the biological markers of cancer. In addition, exosomes could be collected in serum, tissue fluid and urine for diseases follow-up, and urine as the biosample is easier to repeatedly obtain and non-invasive. In this study, the investigators enroll patients with papillary, follicular, and collect the urine samples before operation, immediately after operation, post-operatively. The investigators try to analyze the urinary exosomal proteins to find the early prognostic biological markers in urine via this prospective study.

This pilot study report will explore that urinary exosomal thyroglobulin could be a reliable biological marker to substitute for serum thyroglobulin in the future. Such patient do not need to withdraw thyroid hormone or receive rhTSH stimulation. For patients with thyroid cancer, if they received thyroidectomy with ablative radioactive I-131 therapy, serum thyroglobulin is defined to be cancer biomarker in the course of follow-up. If thyroglobulin cannot be detected in serum, then such patients were suggested to be biochemically complete treatment, independent of the interference of anti-thyroglobulin antibody. Usually, serum thyroglobulin cannot be detected even under expensive rhTSH stimulation in patients of biochemically complete treatment. Therefore, no serial biomarkers could be recorded for evaluation and prediction of cancer recurrence. In this pilot study, urinary exosomal thyroglobulin provides a non-invasive, reproducible, convenient, serial and correct follow-up for patients with thyroid cancer, because the investigators use peptide sequence to quantify the levels of thyroglobulin in urine exosome. Significant reduction in cost-spending in rhTSH consumption, and patients do not need to stop using thyroid hormone during the course of cancer follow-up. In recent years, the progress of peptides mass spectrometry provided a cost-effective, correct and new pathway for the discovery of biomarkers. Large profiling of proteomics of human urine reveled different follow-up manners. In the viewpoints of oncology, one option is to find new biomarkers for earlier diagnosis of various cancers, and the other is to make a breakthrough for follow-up residual tumor and cancer recurrence. The goal of our pilot study is trying to find the new pathway for tracking the biomarker in patients with thyroid cancer receiving ablative surgery and radioactive I-131 treatment.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 3 Years
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population The investigators will enroll 150 post-operative patients with papillary, follicular or anaplastic thyroid cancer, and collect their urine samples in outpatient clinic per year. The investigators will analyze the urine exosomal proteins and probable biological markers, including thyroglobulin and galectin-3. The investigators hope to find the prognostic biological markers via this prospective study. The investigators further hope to find newly therapeutic and follow-up pathway for such patients with well-differentiated or anaplastic thyroid cancer.
Condition Thyroid Cancer
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Huang TY, Wang CY, Chen KY, Huang LT. Urinary Exosomal Thyroglobulin in Thyroid Cancer Patients With Post-ablative Therapy: A New Biomarker in Thyroid Cancer. Front Endocrinol (Lausanne). 2020 Jun 16;11:382. doi: 10.3389/fendo.2020.00382. eCollection 2020.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Actual Enrollment
 (submitted: October 29, 2019)
74
Original Estimated Enrollment
 (submitted: March 28, 2018)
150
Estimated Study Completion Date July 31, 2023
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:diagnosed patients with thyroid papillary, follicular and anaplastic thyroid cancer, post-operation follow up

-

Exclusion Criteria:

  • Unclearly diagnosed patients with thyroid papillary, follicular and anaplastic thyroid cancer
Sex/Gender
Sexes Eligible for Study: All
Ages 20 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number NCT03488134
Other Study ID Numbers 201711082RINA
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party National Taiwan University Hospital
Study Sponsor National Taiwan University Hospital
Collaborators Not Provided
Investigators
Principal Investigator: CHIH-YUAN WANG, Doctor Department of Internal Medicine, National Taiwan University Hospital
PRS Account National Taiwan University Hospital
Verification Date November 2020