Application of Chromosomal Instability in Early Diagnosis of Biliary Tract Carcinoma

Biliary Tract Carcinoma Clinical Trial

Official title:

Application of Chromosomal Instability and Metagenomic Detection in Early Diagnosis of Biliary Tract Carcinoma in Bile

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05845554
• Other study ID #: BileCAD-330
• Status: Recruiting
• Start date: March 30, 2023
• Est. completion date: April 1, 2024

Study information

• Verified date: December 2023
• Source: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
• Contact: fabiao zhang
• Phone: 13706760105
• Email: zhangfabiao[@]enzemed.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from cast-off cells in bile samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of biliary tract carcinoma patients. CIN can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. The investigators here intend to study whether a new method named Bile Ultrasensitive Chromosomal Aneuploidy Detection (BileCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN and microbial infection analysis thus help diagnosing and treating biliary tract carcinoma patients.

Description:

Biliary tract carcinoma account for about 3% of all digestive system tumors, with potential high metastasis and invasion ability. Their early clinical symptoms lack specificity, and they are often found in late stage with poor prognosis. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially way to detect CIN in the cast-off cells from the bile samples for diagnosing and monitoring biliary tract carcinoma patients. BileCAD is a new method to detecting CIN in the DNA sample from patients, including extracting DNA from bile, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of biliary tract carcinoma patients.The investigators intended to conduct a prospective study by analyzing bile samples from gallbladder cancers and cholangiocarcinoma patients and control groups that without any tumor in the Bile duct and gallbladder or other organs to compare the specificity and sensitivity of BileCAD test for diagnosing biliary tract carcinoma to other modalities, such as pathological diagnosis. At the same time, the consistency of BileCAD microbial analysis results and clinical microbial culture results was compared, so as to provide more reference for clinical diagnosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: April 1, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• No systemic therapy or biliary tract surgery before the trial.
• Gallstones, bile duct space, obstructive jaundice and other suspected patients with biliary tract carcinoma.
• Male or female patients aged >= 18 years.
• Participants signed informed consent form.

Exclusion Criteria:

• Age under 18 years.
• Individuals unwilling to sign the consent form or unwilling to provide the medical record.
• Individuals unwilling to participate in this trial.
• Individuals has any active autoimmune disease or history of autoimmune disease.
• Individuals have cardiac clinical symptoms or diseases that are not well controlled.
• Individuals have uncontrolled severe cerebrovascular, pulmonary and other diseases.

Related Conditions & MeSH terms

• Biliary Tract Carcinoma
• Carcinoma
• Chromosomal Instability

Intervention

Diagnostic Test:
• The extracted DNA from bile samples will be analyzed by BileCAD to determine the level of CIN.
The extracted gDNA from bile sample will be analyzed by BileCAD to determine the level of CINs.

Locations

Country	Name	City	State
China	Sir Run Run Shaw Hospital, School of Medicine,Zhejiang University	Hangzhou	Zhejiang
China	Taizhou First People's Hospital	Taizhou	Zhejiang
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang

Sponsors (4)

Lead Sponsor	Collaborator
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University	First Affiliated Hospital of Wenzhou Medical University, Sir Run Run Shaw Hospital, Taizhou First People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Al-Rawi DH, Bakhoum SF. Chromosomal instability as a source of genomic plasticity. Curr Opin Genet Dev. 2022 Jun;74:101913. doi: 10.1016/j.gde.2022.101913. Epub 2022 May 5. — View Citation

Bach DH, Zhang W, Sood AK. Chromosomal Instability in Tumor Initiation and Development. Cancer Res. 2019 Aug 15;79(16):3995-4002. doi: 10.1158/0008-5472.CAN-18-3235. Epub 2019 Jul 26. — View Citation

Liu Y, Yeh MM. Bile duct dysplasia and associated invasive carcinoma: clinicopathological features, diagnosis, and practical challenges. Hum Pathol. 2023 Feb;132:158-168. doi: 10.1016/j.humpath.2022.06.012. Epub 2022 Jun 14. — View Citation

Onoyama T, Matsumoto K, Koda H, Yamashita T, Kurumi H, Kawata S, Takeda Y, Harada K, Yashima K, Isomoto H. Diagnostic usefulness of KL-6 concentration of bile in biliary tract cancer. Mol Clin Oncol. 2018 Apr;8(4):561-566. doi: 10.3892/mco.2018.1571. Epub 2018 Feb 12. — View Citation

Richardson TE, Walker JM, Abdullah KG, McBrayer SK, Viapiano MS, Mussa ZM, Tsankova NM, Snuderl M, Hatanpaa KJ. Chromosomal instability in adult-type diffuse gliomas. Acta Neuropathol Commun. 2022 Aug 17;10(1):115. doi: 10.1186/s40478-022-01420-w. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of bile sample analysis by BileCADanalysis	Number of patients "declared positive" with the BileCAD test among the patients suffered from biliary tract carcinoma.	12 months
Primary	Specificity of bile sample analysis by BileCADanalysis	Number of patients "declared negative" with the BileCAD test among the patients without cancer.	12 months
Secondary	BileCAD microbial analysis results	Consistency of BileCAD microbial analysis results with clinical microbial culture results	12 months
Secondary	BileCAD analyzed the sensitivity of different types and locations of malignant tumors	The tumors were classified into different types and sites and the sensitivity of BileCAD to different types and sites of malignant tumors was calculated.	12 months