Blood test using cfDNA methylation to screen for biliary tract cancers

A Cell-free DNA Methylation Liquid Biopsy for Diagnosis and Management of Biliary Tract Cancers

This study tests whether a blood test that reads cfDNA methylation can detect biliary tract cancers early in adults with or suspected of having these cancers.

Quick facts

• Study type: Observational
• Enrollment: 1800 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07176962 on ClinicalTrials.gov

What this trial studies

Biliary tract cancers are aggressive tumors that are often diagnosed late and have very poor five-year survival. This observational study collects blood from adults with pathologically confirmed biliary tract carcinoma and from patients with other gastrointestinal malignancies to develop and internally validate a cfDNA methylation liquid biopsy. Investigators will profile circulating tumor DNA methylation patterns, build diagnostic models using training and validation cohorts, and compare results to pathology and clinical data. Blood draws and clinical data collection occur at participating tertiary hospitals in China.

Who should consider this trial

Good fit: Adults aged 18–80 with pathologically confirmed biliary tract carcinoma (any TNM stage) who can provide blood samples and meet basic organ function and performance-status criteria.

Not a fit: People outside the 18–80 age range, those unable to provide blood, or those with significant organ dysfunction or poor performance status may not benefit from participation.

Why it matters

Potential benefit: If successful, the test could enable earlier, less invasive detection of biliary tract cancers and increase the number of patients eligible for curative treatment.

How similar studies have performed: ctDNA methylation liquid biopsies have shown promising sensitivity and specificity for early detection in several cancers, but application specifically to biliary tract cancers is relatively novel and has limited large-scale validation to date.

Eligibility criteria

Inclusion Criteria Internal Training and Validation Cohorts

* BTC patients

  1. Willing to voluntarily participate and able to comply with study procedures; if unable to read or sign, informed consent must be signed by a legally authorized representative (LAR).
  2. Age 18-80 years (inclusive).
  3. Able to provide required blood samples.
  4. Pathologically confirmed biliary tract carcinoma (TNM stage I-IV).
  5. Stable vital signs; ECOG performance status 0-1.
  6. Adequate organ function: AST/ALT ≤ 5 × ULN; Child-Pugh class A or B; WBC \> 3 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L; Hemoglobin ≥ 90 g/L; Creatinine clearance ≥ 60 mL/min; Total bilirubin ≤ 3 × ULN.
* Other gastrointestinal malignancies (to exclude BTC non-specific signals)

  1. Voluntary participation with signed informed consent (or by LAR).
  2. Age 18-80 years (inclusive).
  3. Able to provide required blood samples.
  4. Pathologically confirmed gastrointestinal malignancies other than BTC, including hepatocellular carcinoma, gastric cancer, colorectal cancer, and pancreatic cancer (TNM stage I-IV).
  5. Stable vital signs; ECOG performance status 0-1.
* Non-cancer participants (benign biliary disease)

  1. Able to provide written informed consent.
  2. Able to provide required blood samples.
  3. Age 18-80 years (inclusive).
  4. Pathologically or clinically diagnosed benign biliary diseases, including cholecystitis, cholelithiasis, choledocholithiasis, adenomyomatosis, gallbladder polyps, xanthogranulomatous cholecystitis, or primary sclerosing cholangitis.

External Validation Cohorts

* BTC patients

  1. Voluntary participation with signed informed consent (or by LAR).
  2. Imaging findings of malignant biliary stricture or mass, or serum CA19-9 \> 100 U/mL, highly suspicious for BTC, with planned surgery or biopsy for pathological confirmation.
  3. Age 18-80 years (inclusive).
  4. Able to provide required blood samples.
  5. Stable vital signs; ECOG performance status 0-1.
  6. Adequate organ function: AST/ALT ≤ 5 × ULN; Child-Pugh class A or B; WBC \> 3 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L; Hemoglobin ≥ 90 g/L; Creatinine clearance ≥ 60 mL/min; Total bilirubin ≤ 3 × ULN.
* Healthy volunteers

  1. Able to provide written informed consent.
  2. Able to provide required blood samples.
  3. Age 18-80 years (inclusive).

Exclusion Criteria Training and Validation Cohorts

* Cancer patients

  1. Pregnant or breastfeeding women.
  2. History of organ transplantation or prior allogeneic bone marrow/stem cell transplantation.
  3. Blood transfusion within 7 days prior to blood collection.
  4. History of curative cancer treatment within 3 years prior to blood collection.
  5. Use of anti-tumor drugs within 30 days prior to blood collection.
  6. Known bleeding disorders.
  7. Known autoimmune diseases.
  8. Concurrent other malignancies or multiple primary tumors.
* Non-cancer participants

  1. Pregnant or breastfeeding women.
  2. History of organ transplantation or prior allogeneic bone marrow/stem cell transplantation.
  3. Blood transfusion within 7 days prior to blood collection.
  4. History of any malignant tumor.
  5. Known bleeding disorders.
  6. Known autoimmune diseases.
  7. Clinically significant abnormalities on routine examination (excluding hepatitis, hepatic cysts, or benign pulmonary nodules).

External Validation Cohorts

* Cancer patients

  1. Pregnant or breastfeeding women.
  2. History of organ transplantation or prior allogeneic bone marrow/stem cell transplantation.
  3. Blood transfusion within 7 days prior to blood collection.
  4. History of or ongoing curative cancer treatment within 3 years prior to blood collection.
  5. Use of anti-tumor drugs within 30 days prior to blood collection.
  6. Known bleeding disorders or autoimmune diseases.
  7. Concurrent other malignancies (including multiple primaries) or known cancer susceptibility gene carriers.
  8. Pathology confirmed benign disease after biopsy/surgery.
  9. Failure to confirm malignancy by pathology or imaging within 42 days after blood collection, or unclear lesion site/evidence.
  10. Special exclusion criteria:
* Pathology confirmed precancerous lesions.
* Any local/regional or systemic anti-tumor therapy (including surgery, radiotherapy, targeted therapy, or immunotherapy) prior to blood collection.
* Healthy volunteers

  1. Pregnant or breastfeeding women.
  2. History of organ transplantation or prior allogeneic bone marrow/stem cell transplantation.
  3. Blood transfusion within 7 days prior to blood collection.
  4. History of any malignant tumor.
  5. Known bleeding disorders or autoimmune diseases.
  6. Clinically significant abnormalities on health examination (excluding hepatitis, hepatic cysts, or benign pulmonary nodules).

Where this trial is running

Shanghai, Shanghai Municipality

• Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yingbin Liu, PhD — RenJi Hospital
• Study coordinator: Yingbin Liu, PhD

Conditions Gall Bladder Cancer; Intrahepatic Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Hilar Cholangiocarcinoma; Billiary Track Cancer; ctDNA; ctDNA methylation; Early diagnosis