a PROspective Case Control Study to Develop and Validate a Blood Test FOr mUlti-caNcers Early Detection（PROFOUND） (PROFOUND)

PROFOUND Study: Development and Validation of a Multi-cancer Early Detection Model Based on Peripheral Blood Multi-omic Analysis and Machine Learning: a Multicenter, Prospective, Observational, Case-control Study

This study is a multi-center, case-control study aiming at developing and blinded testing machine learning-based multiple cancers early detection model by prospectively collecting blood samples from newly diagnosed cancer patients and individuals without confirmed cancer diagnosis.

Study Overview

• Status: Recruiting
• Conditions: Cancer

Detailed Description

Blood samples from newly diagnosed cancer patients and individuals without confirmed cancer diagnosis will be prospectively collected to identify cancer-specific circulating signals through integrative multi-omic analysis. Based on the comprehensive molecular profiling, a machine learning-driven model will be trained and blinded validated independent through a two-stage approach in clinically annotated individuals. Approximately 10327 cancer patients will be enrolled in this study and early-stage cancer patients will be enriched to improve the model sensitivity on distinguishing cancers with favorable prognosis. Approximately 6339 age and sex matched controls will be included in model development, which are volunteers without a cancer diagnosis after routine cancer screening tests.

• Study Type: Observational
• Enrollment (Estimated): 16666

Contacts and Locations

• Study Contact: Name: Yong Qin; Phone Number: +86 186 2629 2273; Email: qinyong@bytedance.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Jun Wang
    • Beijing, Beijing, China, 100083
      • Not yet recruiting
      • Peking University Cancer Hospital and Institute
      • Contact: Ziyu Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Confirmed cancers or individuals without confirmed cancer will be invited to participate in this case-control study by a designated consenting professional.

Description

Inclusion Criteria for Case Arm Participants:

• 40-74 years old
• Clinically and/or pathologically diagnosed cancer
• No prior or undergoing any systemic or local antitumor therapy, including but not limited to surgical resection, radiochemotherapy, endocrinotherapy, targeted therapy, immunotherapy, interventional therapy, etc.
• Able to provide a written informed consent and willing to comply with all part of the protocol procedures

Exclusion Criteria for Case Arm Participants:

• Pregnancy or lactating women
• Known prior or current diagnosis of other types of malignancies comorbidities
• Severe acute infection (e.g. severe or critical COVID-19, sepsis, etc.) or febrile illness (body temperature of ≥ 38.5 °C) within 14 days prior to screen
• Recipients of organ transplant or prior bone marrow transplant or stem cell transplant
• Recipients of blood transfusion within 30 days prior to screen
• Recipients of therapy in past 14 days prior to screen, including oral or IV antibiotics, glucocorticoid, azacitidine, decitabine, procainamide, hydrazine, arsenic trioxide
• Unsuitable for this trial determined by the researchers

Inclusion Criteria for Control Arm Participants:

• 40-74 years old
• Without confirmed cancer diagnosis
• Able to provide a written informed consent and willing to comply with all part of the protocol procedures

Exclusion Criteria for Control Arm Participants:

• Pregnancy or lactating women
• Known prior or current diagnosis of other types of malignancies comorbidities
• Severe acute infection (e.g. severe or critical COVID-19, sepsis, etc.) or febrile illness (body temperature of ≥ 38.5 °C) within 14 days prior to screen
• Recipients of organ transplant or prior bone marrow transplant or stem cell transplant
• Recipients of blood transfusion within 30 days prior to screen
• Recipients of therapy in the past 14 days prior to screen, including oral or IV antibiotics, glucocorticoid, azacitidine, decitabine, procainamide, hydrazine, arsenic trioxide
• Unsuitable for this trial determined by the researchers

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case arm; Participants with newly diagnosed cancer of lung, breast, digestive tract, urinary tract and etc.
Control arm; Participants without a cancer diagnosis after routine cancer screening tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The performance of cfDNA methylation-based multiple cancers early detection model in case-control study	The sensitivity, specificity and tissue origin accuracy of cfDNA methylation-based multiple cancers early detection model in detecting cancer or non-cancer at 95% confidence interval.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The performance of cfDNA methylation-based multiple cancers early detection model in early stage cancer cases	The sensitivity and tissue origin accuracy of cfDNA methylation-based multiple cancers early detection model in detecting stage I to II cancer at 95% confidence interval.	12 months
The performance of multi-omic-based multiple cancers early detection model in case-control study	The sensitivity, specificity and tissue origin accuracy of multi-omic-based multiple cancers early detection model in detecting cancer or non-cancer at 95% confidence interval.	12 months
The performance of different multi-cancer early detection models in different subgroups	The sensitivity and specificity of cfDNA methylation-based or multi-omic-based multiple cancers early detection model in different subgroups of the population (such as age, gender, cancer pathological classification, and clinical stage) at 95% confidence interval.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To develop a questionnaire to evaluate the risk factors in the multi-cancer early screening	To develop a questionnaire to evaluate the high-risk factors in the multi-cancer early screening, including lung cancer, gastrointestinal cancer, gynecological cancer, urogenital neoplasms, etc.	12 months
To evaluate the performance of multi-omics early detection models in the population with suspected cancer	The sensitivity, specificity and tissue origin accuracy of multi-omic-based multiple cancers early detection model in in the population with suspected cancer at 95% confidence interval.	12 months
To simulate the positive predictive value and negative predictive value of different multi-cancer early detection models based on the cancer prevalence and staging data of individuals aged 40-75 years in China using multiple models	To simulate the positive predictive value and negative predictive value of different multi-cancer early detection models（cfDNA methylation-based or multi-omic-based)，based on the sensitivity, specificity and tissue origin accuracy，according to multi cancer prevalence and staging data of individuals aged 40-75 years in China.	12 months
To simulate the benefits of clinical utility and health economics using different multi-cancer early detection models	To simulate the stage-shift and incremental cost-effective ratio (ICER) benefit when compared to usual care (SOC screening) using Markov model based on MCED test performance	12 months
To explore biomarkers for cancer screening and construct a multimodal machine learning model based on multi-omics data	Exploring biomarkers in methylomics and fragmentomics，and constructing multimodal for multi-cancer early detection based on multiomics analysis	12 months

Collaborators and Investigators

• Sponsor: Shanghai Weihe Medical Laboratory Co., Ltd.
• Collaborators: Peking University People's Hospital
• Investigators: Principal Investigator: Jun Wang, Peking University People's Hospital; Study Director: Xiaohui Wu, Shanghai Weihe Medical Laboratory Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Estimated): January 23, 2024

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: cell-free DNA; methylation; cancer early detection
• Other Study ID Numbers: PROFOUND

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