TRACE-BTC. Relation of Biomarkers and Patients Reported Quality of Life to Outcomes in Patients With Biliary Tract Cancer: a Real- World Cohort

NCT07454486 | Not Yet Recruiting DMC

• 2 other identifiers: 1-16-02-446-241-10-72-152-24
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose of the Study: Bile duct cancers are rare and aggressive. About 250 new cases are diagnosed each year in Denmark. These cancers are difficult to detect early, so only about 20% of patients can have surgery when diagnosed. Even after surgery, the cancer often returns, and chemotherapy only slightly reduces the risk of relapse. For patients who cannot have surgery, treatments such as chemotherapy (sometimes combined with immunotherapy) can relieve symptoms and extend life, but their effect is limited. A small number of patients have specific genetic changes in their cancer that can be treated with targeted medicines. Currently, doctors cannot predict which patients will benefit from treatment. Standard monitoring methods like CT scans are expensive, inconvenient, and sometimes unreliable because bile ducts are hard to see clearly on scans. Blood tests that detect cancer DNA in the blood (called circulating tumor DNA or ctDNA) and other biological markers may be a better way to monitor the disease and adjust treatment. These tests could help detect cancer recurrence earlier and determine whether treatment is working. Measuring patients' quality of life and symptoms over time may also help predict treatment benefit and evaluate effectiveness. The goal of this study is to:

• Investigate how biomarkers, including ctDNA, can predict disease course, detect relapse, and monitor treatment response.
• Identify the best way to measure ctDNA in patients with bile duct cancer.
• Examine whether patients' own reports of quality of life and symptoms can help assess treatment effect and prognosis. Study Design and Procedures: This is a prospective cohort study focusing on blood biomarkers and patient-reported symptoms and quality of life. Participants agree to provide blood samples:
• Before treatment
• During treatment
• During follow-up Each sample involves up to 40 ml of blood, with a maximum of 20 samples per patient. The blood will be analyzed for:
• ctDNA and genetic changes
• Cancer-related markers
• Inflammation markers
• Immune system markers Tumor tissue samples will also be examined to compare blood and tissue results. Full genome or exome sequencing will not be performed. Samples will be stored in a research biobank. For patients with incurable disease, quality of life and symptom burden will be monitored repeatedly using Danish questionnaires. Participants: The study will include:
• Up to 100 patients with potentially curable disease
• Up to 200 patients with incurable disease To participate, patients must:
• Have confirmed bile duct cancer
• Be eligible for curative, additional (adjuvant), or palliative treatment
• Be over 18 years old
• Provide written and verbal consent Patients cannot participate if they:
• Had another cancer within the past 5 years (except early skin cancer or very early cervical cancer)
• Cannot safely provide blood samples
• Are unable to cooperate with study procedures Risks and Inconveniences: Participants will have extra blood samples taken, usually during regular hospital visits. Possible side effects include mild soreness or small bruises at the needle site. The extra blood amount (40 ml per sample) is considered medically insignificant. Participants will also spend time filling out questionnaires. The number and frequency of questions have been kept as low as possible while still providing meaningful data. Financial Information: Extra costs for blood sampling, laboratory analysis, and data collection will be covered by external research funding managed by Aarhus University Hospital. The researchers have no financial interest in the project. Patients will not receive financial compensation for participating. Recruitment and Consent: Potential participants are identified during routine clinical care. During a planned meeting with a doctor, patients receive written and verbal information about the study, including its purpose, risks, advantages, and disadvantages. The conversation takes place in a calm and private setting. Patients may bring a support person. They have time to ask questions and at least 24 hours to consider participation. Patients can withdraw their consent at any time without affecting their treatment. Consent must be given before any study-related procedures begin. Publication of Results: The results - whether positive or negative - will be presented at national and international conferences and submitted to peer-reviewed scientific journals. Ethical Considerations: All participants receive standard medical treatment. The risks and disadvantages are limited, and participants are unlikely to benefit directly from the study. However, the research may improve how biomarkers and patient-reported outcomes are used to predict prognosis and treatment response, potentially leading to better treatment for future patients with bile duct cancer.

Conditions

Biliary Tract Cancer (BTC); Cholangiocarcinoma; Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Resectable; Cholangiocarcinoma Metastatic; Cholangiocarcinoma of the Bile Duct; Cholangiocarcinoma, Extrahepatic; Biliary Tract Cancer (CCA); Gall Bladder Cancer; Biliary Tract Cancers (BTC); Cholangiocarcinoma, Hilar; Cholangiocarcinoma, Intrahepatic; Cholangiocarcinoma, Perihilar; Cholangiocarcinoma; Liver

Keywords

Biliary Tract Neoplasms; Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Gallbladder Neoplasms; Circulating Tumor DNA; Liquid Biopsy; Minimal Residual Disease; Biomarkers, Tumor; Observational Study; Biobanking; DNA Methylation; Precision Oncology

Outcome Measures

Primary Outcomes (2)

• Disease-free survival (DFS)

  Defined as a prognosis-related endpoint used to evaluate the clinical utility of ctDNA assessments. Applied particularly in patients treated with curative intent (e.g., MRD detection, recurrence prediction).

  From enrollment to the end of 5-years follow up period.

• Overall survival (OS)

  Explicitly stated as a prognosis-related endpoint. Used to assess correlation between ctDNA characteristics (quantitative and molecular) and clinical outcomes.

  From enrollment to the end of 5-years follow up period.

Secondary Outcomes (12)

• Recurrence-related outcomes 1

  From enrollment to the end of 5-years

• Recurrence-related outcomes 2

  From enrollment to 5 years

• Recurrence-related outcomes 3

  From enrollment to 5 years

• Treatment response outcomes

  From enrollment through 2 years

• ctDNA methodological comparison outcomes (Concordance Outcome)

  From enrollment through 2 years

Study Arms (3)

Downstaging treatment group

Patients who are planned to recieve downstaging systemic oncological treatment for their biliary tract cancer with the aim for radical local treatment.

Adjuvant treatment group

Patients who are planned to recieve adjuvant treatment after surgery for their biliary tract cancer.

Palliative treatment group

Patients who are planned to recieve palliative systemic oncological treatment for their biliary tract cancer.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will be selected from adult patients with histopathologically verified BTC-or those defined as having BTC by a Multidisciplinary Team (MDT) conference-who are candidates for curative (including downstaging and adjuvant) or palliative treatment and who have no contraindications to blood sampling. Patients are identified in routine clinical practice and referred for oncological management. Patients will be recruited prospectively as they are seen in daily clinical care at participating oncology centers. Eligible individuals must be able to provide written and oral informed consent. The population therefore includes patients across the disease spectrum (localized, locally advanced, or metastatic BTC) undergoing standard-of-care treatments such as surgery, systemic therapy, interventional procedures, or surveillance, with no alteration of therapy due to study participation.

You may qualify if:

• Histopathologically verified biliary tract cancer (BTC) and/or Multidisciplinary Team (MDT) conference decision to define the patient as suffering from BTC.
• Eligible for curative, adjuvant, or palliative oncological treatment.
• Age ≥ 18 years.
• Written and oral consent.

You may not qualify if:

• Other malignant diseases within 5 years of BTC diagnosis, excluding early-stage non-melanoma skin cancer and carcinoma in situ of the cervix.
• Conditions that prohibit blood sampling.
• Known or suspected non-compliance.

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8220, Denmark

Location

Related Publications (22)

• Andersen, L.B., et al. The Clinical Impact of Methylated Homeobox A9 ctDNA in Patients with Non-Resectable Biliary Tract Cancer Treated with Erlotinib and Bevacizumab. Cancers (Basel), 2022;14(19). PMCID: PMC9565119

  BACKGROUND

• Liu, H., Yang, H., and Chen, X. Prognostic Value of Circulating Tumour DNA in Asian Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Evidence-Based Complementary and Alternative Medicine, 2022;2022:8019652. PMCID: PMC9260106

  BACKGROUND

• Guven, D.C., et al. A systematic review and meta-analysis of the association between circulating tumor DNA (ctDNA) and prognosis in pancreatic cancer. Critical Reviews in Oncology/Hematology, 2021;168:103528. PMID: 34678555

  BACKGROUND

• Friend, E., et al. Development of a questionnaire (EORTC module) to measure quality of life in patients with cholangiocarcinoma and gallbladder cancer, the EORTC QLQ-BIL21. British Journal of Cancer, 2011;104(4):587-592. PMCID: PMC3046617

  BACKGROUND

• Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.

  PMID: 8433390 BACKGROUND

• Marschner, N., et al. Association of Disease Progression With Health-Related Quality of Life Among Adults With Breast, Lung, Pancreatic, and Colorectal Cancer. JAMA Network Open, 2020;3(3):e200643. PMCID: PMC7052784

  BACKGROUND

• Montazeri, A. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008. Health and Quality of Life Outcomes, 2009;7:102. PMCID: PMC2785823

  BACKGROUND

• Jakobsen, A., et al. Early ctDNA response to chemotherapy. A potential surrogate marker for overall survival. European Journal of Cancer, 2021;149:128-133. PMID: 33887445

  BACKGROUND

• Spindler, K.G., et al. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist, 2017;22(9):1049-1055. PMID: 28674120

  BACKGROUND

• Goyal, L., et al. TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma. Cancer Discovery, 2019;9(8):1064-1079. PMID: 31097588

  BACKGROUND

• Berchuck, J.E., et al. The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Annals of Oncology, 2022;33(12):1269-1283. PMID: 36156151

  BACKGROUND

• Kam, A.E., Masood, A., and Shroff, R.T. Current and emerging therapies for advanced biliary tract cancers. Lancet Gastroenterology & Hepatology, 2021;6(11):956-969. PMID: 34506749

  BACKGROUND

• Idris, R., Chaijaroenkul, W., and Na-Bangchang, K. Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review. Asian Pacific Journal of Cancer Prevention, 2023;24(3):741-751. PMID: 36951263

  BACKGROUND

• Cai, Q.Y., et al. The association of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study. Cancer, 2023;129(19):2999-3009. PMID: 37501546

  BACKGROUND

• Haslam, A., et al. A systematic review of trial-level meta-analyses measuring the strength of association between surrogate end-points and overall survival in oncology. European Journal of Cancer, 2019;106:196-211. PMID: 30665033

  BACKGROUND

• Spindler, K.G. and Jakobsen, A. Circulating tumor DNA: Response Evaluation Criteria in Solid Tumors - can we RECIST? Focus on colorectal cancer. Therapeutic Advances in Medical Oncology, 2023;15:17588359231171580. PMID: 37013177

  BACKGROUND

• Lamarca, A., et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncology, 2021;22(5):690-701. PMID: 33713682

  BACKGROUND

• Oh, D.-Y., et al. Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Lancet Gastroenterology & Hepatology, 2022;7(6):522-532. PMID: 35483072

  BACKGROUND

• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

  PMID: 20375404 BACKGROUND

• Primrose, J.N., et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncology, 2019;20(5):663-673. PMID: 30922733

  BACKGROUND

• Thuehøj, A.U., et al. Clinical outcomes after stereotactic ablative radiotherapy in locally advanced cholangiocarcinoma. Acta Oncologica (Stockholm, Sweden), 2022: 197-201. PMID: 35068250

  BACKGROUND

• The Danish Hepato-biliary Cancer Group. 2022 Annual report from the Danish Hepato-biliary Cancer Database. 2022, The Regional Clinical Quality Programme.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and tissue samples

MeSH Terms

Conditions

Biliary Tract Neoplasms; Gallbladder Neoplasms; Cholangiocarcinoma; Klatskin Tumor; Neoplasm, Residual; Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mohamed Metwally, Consultant, MD, PhD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Karen-Lise Garm Spindler, Professor, MD, PhD

  Aarhus University Hospital

  STUDY CHAIR

• Lise Thorsen, Associate professor, MD, PhD

  Aarhus University Hospital

  STUDY CHAIR

Central Study Contacts

Mohamed Metwally, MD, PhD

CONTACT

+4578454872; hassan@oncology.au.dk

Lise Thorsen, MD, PhD

CONTACT

+45 9116 7617; Lise.Bech.Jellesmark.Thorsen@auh.rm.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant of Clinical Oncology, MD, PhD

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: March 6, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2031
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)