The Unintrusive Detection of EaRly-stage Cancers (THUNDER)

A Blinded Prospective Study on Validation of the Performance of a cfDNA Methylation-based Model for Early Cancer Detection

According to a previous study, a cell-free DNA (cfDNA) methylation-based model showed high sensitivity and specificity (80.6% and 98.3%) in blood-based multi-cancer detection. In this way, a multi-center, prospective, single-blind study (THUNDER study) is designed to further validate the performance of the cfDNA methylation-based model for early cancer detection. Blood RNA markers will also be evaluated. The study will enroll approximately 2508 participants, including participants with malignancies and healthy participants.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Device: Multi-cancer early detection test

• Study Type: Observational
• Enrollment (Actual): 2508

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Eligible participants will be recruited from medical centers and assigned into two arms, including participants with new diagnosis of malignancies and healthy participants.

Description

Inclusion Criteria for All the Participants:

• Ability to provide a written informed consent
• 40-75 years old
• Ability to comply with study procedures

Exclusion Criteria for All the Participants:

• Pregnancy or lactating women
• Recipients of organ transplant or prior non-autologous (allogeneic) bone marrow transplant or stem cell transplant
• Recipients of blood transfusion within 7 days prior to study blood draw
• Recipients of any anti-cancer therapy within 30 days prior to study blood draw, due to diseases other than cancer

Inclusion Criteria for Cancer Arm Participants:

• Confirmed diagnosis or suspicious cases of cancer within 42 days prior to study blood draw.
• No prior anti-cancer therapy (local or systematic) prior to study blood draw

Exclusion Criteria for Cancer Arm Participants:

• Known prior or current diagnosis of other types of malignancies or multiple primary tumors
• Diagnosis of benign diseases by histopathological assessments
• No confirmed diagnosis of cancer by histopathological or radiological assessments within 42 days of study blood draw, or inability to characterize whether the lesion is malignant or benign
• Non-small-cell lung cancer patients with ground-class nodularity by radiological examination
• Diagnosis of precancerous lesions

Inclusion Criteria for Healthy Arm Participants:

• No cancer-related symptoms or discomfort within 30 days prior to study blood draw
• No clinically significant finding by physical examinations, hematological assessment, urinalysis, LDCT or ultrasound
• No clinically significant finding by breast ultrasound or Molybdenum Target Mammography Detection, or Thinprep cytologic test (TCT) detection for female participants
• No active hepatitis B or hepatitis C infection

Exclusion Criteria for Healthy Arm Participants:

• Prior or ongoing treatment of cancer within 3 years prior to study blood draw
• Clinically significant or uncontrolled comorbidities

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cancer Arm; Participants with new diagnosis of cancer, from whom blood samples will be collected	Device: Multi-cancer early detection test; Blood collection and multi-cancer early detection test
Healthy Arm; Participants without known presence of malignancies or benign diseases, from whom blood samples will be collected	Device: Multi-cancer early detection test; Blood collection and multi-cancer early detection test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sensitivity and specificity of early detection of 6 types of cancers and Tissue of origin (TOO) accuracy of a cfDNA methylation-based model	7 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Sensitivity, specificity and TOO accuracy of a cfDNA methylation-based model in different stages or pathological types of cancer	7 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Guangzhou Burning Rock Dx Co., Ltd.
• Investigators: Principal Investigator: Qiang Gao, M.D., Shanghai Zhongshan Hospital

Publications and helpful links

Helpful Links

• Q. Gao, B. Li, S. Cai, et al. Early detection and localization of multiple cancers using a blood-based methylation assay (ELSA-seq). Annals of Oncology (2020) 31 (suppl_6): S1358.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Liquid biopsy; Early detection; Cell-free DNA (cfDNA)
• Other Study ID Numbers: RSCD2020003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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