An Active Surveillance Program for Cases of Medullary Thyroid Carcinoma (MTC)

Medullary Thyroid Carcinoma Surveillance Study: A Case-Series Registry

This study is conducted in the United States of America (USA). The aim of the study is to monitor the number of annual new adult cases of medullary thyroid carcinoma (MTC) and to establish a registry for these new cases in order to identify any possible increase related to the introduction of liraglutide, exenatide once-weekly, and other GLP-1 receptor agonists into the US market.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus, Type 2; Diabetes; Weight Management; Medullary Thyroid Carcinoma
• Intervention / Treatment: Other: No treatment given

Detailed Description

This active surveillance program will monitor for any signal indicating a possible association between treatment with long-acting GLP-1 RAs and the development of MTC in the United States population. Given the very low incidence of MTC in the general population, the expected rate of exposure to long-acting GLP-1 RAs, the anticipated long latency of the potential outcome under study and the limited data on underlying risk factors for development of MTC other than RET proto-oncogene mutations, an active surveillance program is the most efficient means of identifying a possible association between MTC and products in the long-acting GLP-1 RAs class. Given the uncertainty of the association of MTC in humans treated with these drugs, a study duration of at least fifteen years from the time of market introduction of the first long-acting GLP-1 RA was thought to provide evidence of an association, if one exists. If such an association is identified, a case-control study will be initiated to quantify the association.

The MTC registry is a Food and Drug Administration (FDA) post-marketing requirement for long-acting GLP-1 RA products. Because of the rarity of MTC and in order to minimize inconvenience to patients, physicians, and state cancer registries, FDA encouraged sponsors of long-acting GLP-1 RAs to work collaboratively to conduct this registry. Consequently, the MTC Registry Consortium has been formed for this purpose.

The MTC Registry Consortium refers to the Sponsors with approved long-acting GLP-1 RAs who have a contractual agreement to participate in the MTC Registry.

This active surveillance program for cases of MTC will be conducted with assistance from the North American Association of Central Cancer Registries (NAACCR). NAACCR is a collaborative umbrella organization for cancer registries, government agencies, professional organizations, and private groups in North America interested in improving the quality and use of cancer registry data. All of the central cancer registries in the U.S. and Canada are members of NAACCR, including those that participate in SEER.

• Study Type: Observational
• Enrollment (Estimated): 6750

Contacts and Locations

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26505-8065
      • United BioSource, LLC

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

People with medullary thyroid carcinoma invited by either written invitation from the participating cancer registry or the diagnosing physician to participate in the study.

Description

Inclusion Criteria:

• A record of medullary thyroid carcinoma (MTC) identified from state/regional population-based cancer registries
• At least 18 years or older.

There are no other inclusion or exclusion criteria.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Questionnaire; None. Non-interventional study.	Other: No treatment given; None. Non-interventional study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annual incidence of MTC in the US to identify any possible increase related to the introduction of liraglutide, exenatide once-weekly, and other GLP-1 receptor agonists into the US market.	Up to 15 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Family history of cancer (including history of MEN2A or MEN 2B, history of FMTC, history of RET proto-oncogene mutations), Patient demographic characteristics, Patient prior history of thyroid diseases	Up to 15 years
Dose and Duration of use of all previous diabetes medication exposures (including long acting and short acting GLP-1 receptor agonists, DPP4 inhibitors, and insulin)	Up to 15 years
Dose and Duration of use of all previous weight management drugs (including long acting GLP-1 receptor agonists).	Up to 15 years
Lifestyle factors such as smoking and alcohol use	Up to 15 years
Environmental exposures (occupational history, radioiodine exposure, nuclear fallout)	Up to 15 years

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Collaborators: Eli Lilly and Company; AstraZeneca; United BioSource, LLC
• Investigators: Study Director: Annette Stemhagen, DrPH, FISPE, United BioSource, LLC

Publications and helpful links

General Publications

• Major-Pedersen A, McCullen MK, Sabol ME, Adetunji O, Massaro J, Neugut AI, Sosa JA, Hollenberg AN. A joint industry-sponsored data monitoring committee model for observational, retrospective drug safety studies in the real-world setting. Pharmacoepidemiol Drug Saf. 2021 Jan;30(1):9-16. doi: 10.1002/pds.5172. Epub 2020 Nov 24.

Helpful Links

• AstraZeneca Pharmaceuticals LP

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Estimated): December 1, 2039
• Study Completion (Estimated): December 1, 2039

Study Registration Dates

• First Submitted: November 30, 2011
• First Submitted That Met QC Criteria: January 12, 2012
• First Posted (Estimated): January 18, 2012

Study Record Updates

• Last Update Posted (Actual): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: semaglutide; liraglutide; GLP1; Glucagon like peptide; exenatide extended release; dulaglutide; semaglutide tablets
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Diabetes Mellitus; Diabetes Mellitus, Type 2; Carcinoma; Thyroid Diseases; Thyroid Neoplasms; Carcinoma, Neuroendocrine
• Other Study ID Numbers: NN2211-3965; U1111-1125-4362 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Currently this is undecided for this 15 year registry. The Data Monitoring Committee is a group of external interdisciplinary consultants who oversee the registry data to review if there are any signals or safety concerns with patients who have taken any of the long-acting GLP-1 RAs and were diagnosed with medullary thyroid carcinoma.