Biliary Tract Cancer (BTC)TRACE-BTCNCT07454486
TRACE-BTC. Relation of Biomarkers and Patients Reported Quality of Life to Outcomes in Patients With Biliary Tract Cancer: a Real- World Cohort
An observational study of Biliary Tract Cancer (BTC) and Biliary Tract Cancer (CCA), run by Aarhus University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Biliary Tract Cancer (BTC), Biliary Tract Cancer (CCA), Gall Bladder Cancer
- How many people
- 300 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Mar 2026to 30 Dec 2031
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site
Aarhus University Hospital
Aarhus, 8220
Mohamed Metwally, MD, Consultant, PhD, +4578454872, hassan@oncology.au.dk
Lise Thorsen, Associate professor, MD, PhD, +45 9116 7617, Lise.Bech.Jellesmark.Thorsen@auh.rm.dk
About this study
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.
Read more
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.
Read the detailed description
This prospective, non-interventional observational study investigates the longitudinal dynamics of circulating tumor DNA (ctDNA), circulating biomarkers, and patient-reported outcomes in patients with biliary tract cancer (BTC) undergoing standard oncological treatment in routine clinical practice. The study is conducted across participating oncology centers and integrates translational laboratory analyses with structured clinical and patient-reported data collection.
# Study Design and Population
Participants are enrolled consecutively from the clinical population of patients diagnosed with BTC and assessed for curative-intent (including adjuvant or downstaging strategies) or palliative oncological treatment. Inclusion occurs within routine care pathways, and study participation does not influence treatment allocation, clinical decision-making, or follow-up schedules. All therapeutic interventions are delivered according to institutional standards and national guidelines.
# Longitudinal Sampling Framework
Peripheral blood samples are collected at predefined clinically relevant milestones across the treatment trajectory, including baseline, during systemic therapy, perioperative periods (if applicable), response evaluation, and follow-up. Sampling schedules are protocolized and may be reset if treatment strategy changes to ensure temporal alignment with clinical course. Each sampling allows collection of up to 40 mL of blood, with a maximum of 20 study-related samples per participant over the study period.
Specimens are processed using standardized pre-analytical workflows and stored at -80°C in a central research biobank. Temporary local storage at participating sites (maximum 5-7 days) is permitted prior to shipment to the central biobank under controlled conditions. All samples are pseudonymized using unique study identifiers.
# Translational Research Program
Retrospective batch analyses are performed on centrally stored plasma samples to ensure methodological consistency and reduce analytical variability. The translational laboratory program includes:
- Tumor-informed and tumor-uninformed ctDNA assays
- Detection of single nucleotide variants, indels, copy number alterations, and gene fusions
- Targeted methylation marker analyses
- Comparative analyses between plasma-derived biomarkers and archival tumor tissue
- Immunohistochemical characterization of tumor tissue when available
- Exploratory assessment of additional circulating biomarkers related to tumor burden, inflammation, and immune status
Whole-genome and whole-exome sequencing are not performed. All laboratory analyses follow validated, standardized workflows and are conducted at accredited academic laboratory facilities, including Aarhus University Hospital and collaborating molecular diagnostic laboratories.
# Patient-Reported Outcomes
Health-related quality of life (HRQoL) is assessed longitudinally using validated Danish-language instruments at predefined time points aligned with treatment and follow-up visits. Questionnaire burden is minimized while maintaining methodological robustness. PROM data are integrated with clinical and biomarker datasets to enable exploratory analyses of associations between biological markers and patient-reported outcomes.
- Data Collection and Management
Clinical data are extracted from electronic medical records and entered into a secure, centralized REDCap database hosted by Aarhus University. The database incorporates role-based access control, audit trails, predefined validation rules, and structured electronic case report forms. All data are pseudonymized, and no study data are recorded prior to written informed consent.
Data sources include routine clinical documentation, laboratory records, and PROM questionnaires. A predefined data dictionary ensures standardized variable definitions, harmonized terminology, and reproducibility across sites.
# Quality Assurance and Governance
The study is centrally coordinated and conducted in accordance with standardized operating procedures covering consent procedures, biospecimen handling, laboratory workflows, data entry, and protocol deviation management. Automated validation rules, logical consistency checks, and periodic internal data reviews are implemented to ensure data quality and completeness. Source data verification is supported by audit trails and controlled access to medical records for authorized personnel.
# Statistical and Analytical Approach
Analyses focus on the association between ctDNA dynamics, clinical variables, and outcomes. The statistical framework includes descriptive analyses, correlation analyses, survival modeling using Kaplan-Meier methods, and multivariable Cox regression to adjust for relevant clinical confounders. Comparative analyses between plasma-based biomarkers and tumor tissue findings will be performed where available. Integration of biomarker data with longitudinal PROM data will be exploratory.
Sample size targets are based on feasibility and predefined translational objectives for curative-intent monitoring, baseline ctDNA detection in advanced disease, and early ctDNA dynamics during treatment.
# Ethical Considerations and Safety
The study involves minimal risk, as the only study-specific procedure is additional peripheral blood sampling. Potential risks are limited to transient discomfort or minor bruising. Participation does not interfere with standard clinical care, and patients may withdraw consent at any time without consequences for treatment.
All biological materials and study data are handled in compliance with applicable data protection legislation and ethical regulations. Residual biological material may be stored for future ethically approved research if separate consent is provided; otherwise, excess material is destroyed after completion of study-specific analyses.
# Study Timeline
Patient inclusion is planned from 2026 through 2030, with longitudinal follow-up and final analyses expected to be completed in 2031. Results will be disseminated through peer-reviewed publications and scientific conferences irrespective of study outcomes.
- Conditions
- Biliary Tract Cancer (BTC), Biliary Tract Cancer (CCA), Gall Bladder Cancer, Biliary Tract Cancers (BTC), Cholangiocarcinoma, Cholangiocarcinoma Non-resectable
- 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
- Medical subject headings
- Biliary Tract Neoplasms, Gallbladder Neoplasms, Cholangiocarcinoma, Klatskin Tumor, Neoplasm, Residual, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: From enrollment to the end of 5-years follow up period.
Secondary outcomes (12)
Recurrence-related outcomes 1
Association between post-treatment MRD status (positive vs negative) and recurrence-free survival
Measured: From enrollment to the end of 5-years
Recurrence-related outcomes 2
Association between ctDNA elimination pattern and recurrence-free survival
Measured: From enrollment to 5 years
Recurrence-related outcomes 3
Association between quantitative ctDNA levels during follow-up and recurrence risk
Measured: From enrollment to 5 years
Treatment response outcomes
Association between percent change in ctDNA level from baseline and objective response rate (RECIST 1.1) during palliative systemic therapy
Measured: From enrollment through 2 years
ctDNA methodological comparison outcomes (Concordance Outcome)
Concordance rate between NGS-based and ddPCR-based ctDNA detection (positive vs negative)
Measured: From enrollment through 2 years
ctDNA methodological comparison outcomes (Quantitative Correlation)
Correlation between ctDNA levels measured by NGS and ddPCR
Measured: From enrollment through 2 years
Prognostic correlations with ctDNA characteristics 1
Association between baseline ctDNA level and recurrence-free survival
Measured: From enrollment through 2 years
Prognostic correlations with ctDNA characteristics 2
Association between ctDNA elimination during curative treatment (cleared vs persistent) and recurrence-free survival
Measured: From enrollment through 2 years
HRQoL (PROMs)-related outcomes 1
Association between baseline HRQoL score (EORTC QLQ-C30 global health status score) and overall survival
Measured: From enrollment through 2 years
HRQoL (PROMs)-related outcomes 2
Association between clinically significant deterioration in HRQoL (≥10-point decrease in EORTC QLQ-C30 global health score) and overall survival
Measured: From enrollment through 2 years
Treatment resistance outcome 1
Association between ctDNA clearance at 8 weeks (undetectable vs detectable) and objective treatment resistance (progressive disease by RECIST 1.1)
Measured: From enrollment through 2 years
Treatment resistance outcome 2
Correlation between percent increase in ctDNA levels during therapy and time to progression
Measured: From enrollment through 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study start15 Mar 2026 (estimated)
- Primary completion30 Dec 2030 (estimated)
- Study completion30 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract Cancer (BTC)Studies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Metwally, Aarhus University Hospital
- Investigators
- Mohamed Metwally, Consultant, MD, PhD, Principal investigator, Aarhus University HospitalKaren-Lise Garm Spindler, Professor, MD, PhD, Study chair, Aarhus University HospitalLise Thorsen, Associate professor, MD, PhD, Study chair, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07454486
- Sponsor's protocol ID
- 1-16-02-446-24
- Other IDs
- 1-10-72-152-24
- Acronym
- TRACE-BTC
- Status last verified
- Mar 2026
- First submitted
- 23 Feb 2026
- Last updated
- 6 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared due to ethical, legal, and privacy considerations. The dataset contains sensitive clinical information, biomarker results (including ctDNA analyses), and patient-reported outcomes that could potentially allow re-identification of participants despite pseudonymization. Data collection and storage are governed by informed consent, data protection regulations, and regional legislation (e.g., GDPR), which restrict the sharing of identifiable or potentially identifiable health data beyond the approved research purposes. Additionally, the consent obtained specifies use of data within the scope of the study and related ethically approved research. Therefore, only aggregated and anonymized results will be reported in publications, and any future data sharing would require additional ethical approval and appropriate data-sharing agreements to ensure participant confidentiality and compliance with applicable regulations.
Publications
Andersen LB, Mahler MSK, Andersen RF, Jensen LH, Raunkilde L. The Clinical Impact of Methylated Homeobox A9 ctDNA in Patients with Non-Resectable Biliary Tract Cancer Treated with Erlotinib and Bevacizumab. Cancers (Basel). 2022 Sep 22;14(19):4598. doi: 10.3390/cancers14194598.
PubMed 36230519Liu H, Yang H, Chen X. Prognostic Value of Circulating Tumour DNA in Asian Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2022 Feb 24;2022:8019652. doi: 10.1155/2022/8019652. eCollection 2022.
PubMed 35251214Guven DC, Sahin TK, Yildirim HC, Aktepe OH, Dizdar O, Yalcin S. A systematic review and meta-analysis of the association between circulating tumor DNA (ctDNA) and prognosis in pancreatic cancer. Crit Rev Oncol Hematol. 2021 Dec;168:103528. doi: 10.1016/j.critrevonc.2021.103528. Epub 2021 Nov 17.
PubMed 34800650Friend E, Yadegarfar G, Byrne C, Johnson CD, Sezer O, Pucciarelli S, Pereira SP, Chie WC, Banfield A, Ramage JK; EORTC Quality of Life Group. Development of a questionnaire (EORTC module) to measure quality of life in patients with cholangiocarcinoma and gallbladder cancer, the EORTC QLQ-BIL21. Br J Cancer. 2011 Feb 15;104(4):587-92. doi: 10.1038/sj.bjc.6606086. Epub 2011 Jan 25.
PubMed 21266979Aaronson 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.
PubMed 8433390Marschner N, Zacharias S, Lordick F, Hegewisch-Becker S, Martens U, Welt A, Hagen V, Gleiber W, Bohnet S, Kruggel L, Dille S, Nusch A, Dorfel S, Decker T, Janicke M. Association of Disease Progression With Health-Related Quality of Life Among Adults With Breast, Lung, Pancreatic, and Colorectal Cancer. JAMA Netw Open. 2020 Mar 2;3(3):e200643. doi: 10.1001/jamanetworkopen.2020.0643.
PubMed 32154886Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008. Health Qual Life Outcomes. 2009 Dec 23;7:102. doi: 10.1186/1477-7525-7-102.
PubMed 20030832Jakobsen A, Andersen RF, Hansen TF, Jensen LH, Faaborg L, Steffensen KD, Thomsen CB, Wen SWC. Early ctDNA response to chemotherapy. A potential surrogate marker for overall survival. Eur J Cancer. 2021 May;149:128-133. doi: 10.1016/j.ejca.2021.03.006. Epub 2021 Apr 12.
PubMed 33857886Spindler KG, Boysen AK, Pallisgard N, Johansen JS, Tabernero J, Sorensen MM, Jensen BV, Hansen TF, Sefrioui D, Andersen RF, Brandslund I, Jakobsen A. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2017 Sep;22(9):1049-1055. doi: 10.1634/theoncologist.2016-0178. Epub 2017 Aug 4.
PubMed 28778958Goyal L, Shi L, Liu LY, Fece de la Cruz F, Lennerz JK, Raghavan S, Leschiner I, Elagina L, Siravegna G, Ng RWS, Vu P, Patra KC, Saha SK, Uppot RN, Arellano R, Reyes S, Sagara T, Otsuki S, Nadres B, Shahzade HA, Dey-Guha I, Fetter IJ, Baiev I, Van Seventer EE, Murphy JE, Ferrone CR, Tanabe KK, Deshpande V, Harding JJ, Yaeger R, Kelley RK, Bardelli A, Iafrate AJ, Hahn WC, Benes CH, Ting DT, Hirai H, Getz G, Juric D, Zhu AX, Corcoran RB, Bardeesy N. TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma. Cancer Discov. 2019 Aug;9(8):1064-1079. doi: 10.1158/2159-8290.CD-19-0182. Epub 2019 May 20.
PubMed 31109923Berchuck JE, Facchinetti F, DiToro DF, Baiev I, Majeed U, Reyes S, Chen C, Zhang K, Sharman R, Uson Junior PLS, Maurer J, Shroff RT, Pritchard CC, Wu MJ, Catenacci DVT, Javle M, Friboulet L, Hollebecque A, Bardeesy N, Zhu AX, Lennerz JK, Tan B, Borad M, Parikh AR, Kiedrowski LA, Kelley RK, Mody K, Juric D, Goyal L. The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Ann Oncol. 2022 Dec;33(12):1269-1283. doi: 10.1016/j.annonc.2022.09.150. Epub 2022 Sep 9.
PubMed 36089135Kam AE, Masood A, Shroff RT. Current and emerging therapies for advanced biliary tract cancers. Lancet Gastroenterol Hepatol. 2021 Nov;6(11):956-969. doi: 10.1016/S2468-1253(21)00171-0.
PubMed 34626563Idris R, Chaijaroenkul W, Na-Bangchang K. Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review. Asian Pac J Cancer Prev. 2023 Mar 1;24(3):741-751. doi: 10.31557/APJCP.2023.24.3.741.
PubMed 36974526Cai QY, Yang P, Yang XL, Zhang XH, Guo LP, Lu XY, Huo L, Ma HB, Wang XD, Zhou HB, Wu L, Jia NY. The association of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study. Cancer. 2023 Oct 1;129(19):2999-3009. doi: 10.1002/cncr.34854. Epub 2023 Jul 14.
PubMed 37449788Haslam A, Hey SP, Gill J, Prasad V. A systematic review of trial-level meta-analyses measuring the strength of association between surrogate end-points and overall survival in oncology. Eur J Cancer. 2019 Jan;106:196-211. doi: 10.1016/j.ejca.2018.11.012. Epub 2018 Dec 5.
PubMed 30528804
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TRACE-BTC. Relation of Biomarkers and Patients Reported Quality of Life to Outcomes in Patients With Biliary Tract Cancer: a Real- World Cohort
- ClinicalTrials.gov ID
- NCT07454486
- Acronym / sponsor ID
- TRACE-BTC / 1-16-02-446-24
- Conditions
- Biliary Tract Cancer (BTC), Biliary Tract Cancer (CCA), Gall Bladder Cancer, Biliary Tract Cancers (BTC), Cholangiocarcinoma, Cholangiocarcinoma Non-resectable
- Keywords
- Biliary Tract Neoplasms, Cholangiocarcinoma, Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma, Gallbladder Neoplasms, Circulating Tumor DNA, Liquid Biopsy, Minimal Residual Disease
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- 15 Mar 2026 (estimated)
- Primary completion
- 30 Dec 2030 (estimated)
- Study completion
- 30 Dec 2031 (estimated)
- First posted
- 6 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This prospective, non-interventional observational study investigates the longitudinal dynamics of circulating tumor DNA (ctDNA), circulating biomarkers, and patient-reported outcomes in patients with biliary tract cancer (BTC) undergoing standard oncological treatment in routine clinical practice. The study is conducted across participating oncology centers and integrates translational laboratory analyses with structured clinical and patient-reported data collection.
# Study Design and Population
Participants are enrolled consecutively from the clinical population of patients diagnosed with BTC and assessed for curative-intent (including adjuvant or downstaging strategies) or palliative oncological treatment. Inclusion occurs within routine care pathways, and study participation does not influence treatment allocation, clinical decision-making, or follow-up schedules. All therapeutic interventions are delivered according to institutional standards and national guidelines.
# Longitudinal Sampling Framework
Peripheral blood samples are collected at predefined clinically relevant milestones across the treatment trajectory, including baseline, during systemic therapy, perioperative periods (if applicable), response evaluation, and follow-up. Sampling schedules are protocolized and may be reset if treatment strategy changes to ensure temporal alignment with clinical course. Each sampling allows collection of up to 40 mL of blood, with a maximum of 20 study-related samples per participant over the study period.
Specimens are processed using standardized pre-analytical workflows and stored at -80°C in a central research biobank. Temporary local storage at participating sites (maximum 5-7 days) is permitted prior to shipment to the central biobank under controlled conditions. All samples are pseudonymized using unique study identifiers.
# Translational Research Program
Retrospective batch analyses are performed on centrally stored plasma samples to ensure methodological consistency and reduce analytical variability. The translational laboratory program includes:
- Tumor-informed and tumor-uninformed ctDNA assays
- Detection of single nucleotide variants, indels, copy number alterations, and gene fusions
- Targeted methylation marker analyses
- Comparative analyses between plasma-derived biomarkers and archival tumor tissue
- Immunohistochemical characterization of tumor tissue when available
- Exploratory assessment of additional circulating biomarkers related to tumor burden, inflammation, and immune status
Whole-genome and whole-exome sequencing are not performed. All laboratory analyses follow validated, standardized workflows and are conducted at accredited academic laboratory facilities, including Aarhus University Hospital and collaborating molecular diagnostic laboratories.
# Patient-Reported Outcomes
Health-related quality of life (HRQoL) is assessed longitudinally using validated Danish-language instruments at predefined time points aligned with treatment and follow-up visits. Questionnaire burden is minimized while maintaining methodological robustness. PROM data are integrated with clinical and biomarker datasets to enable exploratory analyses of associations between biological markers and patient-reported outcomes.
- Data Collection and Management
Clinical data are extracted from electronic medical records and entered into a secure, centralized REDCap database hosted by Aarhus University. The database incorporates role-based access control, audit trails, predefined validation rules, and structured electronic case report forms. All data are pseudonymized, and no study data are recorded prior to written informed consent.
Data sources include routine clinical documentation, laboratory records, and PROM questionnaires. A predefined data dictionary ensures standardized variable definitions, harmonized terminology, and reproducibility across sites.
# Quality Assurance and Governance
The study is centrally coordinated and conducted in accordance with standardized operating procedures covering consent procedures, biospecimen handling, laboratory workflows, data entry, and protocol deviation management. Automated validation rules, logical consistency checks, and periodic internal data reviews are implemented to ensure data quality and completeness. Source data verification is supported by audit trails and controlled access to medical records for authorized personnel.
# Statistical and Analytical Approach
Analyses focus on the association between ctDNA dynamics, clinical variables, and outcomes. The statistical framework includes descriptive analyses, correlation analyses, survival modeling using Kaplan-Meier methods, and multivariable Cox regression to adjust for relevant clinical confounders. Comparative analyses between plasma-based biomarkers and tumor tissue findings will be performed where available. Integration of biomarker data with longitudinal PROM data will be exploratory.
Sample size targets are based on feasibility and predefined translational objectives for curative-intent monitoring, baseline ctDNA detection in advanced disease, and early ctDNA dynamics during treatment.
# Ethical Considerations and Safety
The study involves minimal risk, as the only study-specific procedure is additional peripheral blood sampling. Potential risks are limited to transient discomfort or minor bruising. Participation does not interfere with standard clinical care, and patients may withdraw consent at any time without consequences for treatment.
All biological materials and study data are handled in compliance with applicable data protection legislation and ethical regulations. Residual biological material may be stored for future ethically approved research if separate consent is provided; otherwise, excess material is destroyed after completion of study-specific analyses.
# Study Timeline
Patient inclusion is planned from 2026 through 2030, with longitudinal follow-up and final analyses expected to be completed in 2031. Results will be disseminated through peer-reviewed publications and scientific conferences irrespective of study outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Disease-free survival (DFS)
Time frame: From enrollment to the end of 5-years follow up period.
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).
Overall survival (OS)
Time frame: From enrollment to the end of 5-years follow up period.
Explicitly stated as a prognosis-related endpoint. Used to assess correlation between ctDNA characteristics (quantitative and molecular) and clinical outcomes.
12 secondary outcomes
Recurrence-related outcomes 1
Time frame: From enrollment to the end of 5-years
Recurrence-related outcomes 2
Time frame: From enrollment to 5 years
Recurrence-related outcomes 3
Time frame: From enrollment to 5 years
Treatment response outcomes
Time frame: From enrollment through 2 years
ctDNA methodological comparison outcomes (Concordance Outcome)
Time frame: From enrollment through 2 years
ctDNA methodological comparison outcomes (Quantitative Correlation)
Time frame: From enrollment through 2 years
Prognostic correlations with ctDNA characteristics 1
Time frame: From enrollment through 2 years
Prognostic correlations with ctDNA characteristics 2
Time frame: From enrollment through 2 years
HRQoL (PROMs)-related outcomes 1
Time frame: From enrollment through 2 years
HRQoL (PROMs)-related outcomes 2
Time frame: From enrollment through 2 years
Treatment resistance outcome 1
Time frame: From enrollment through 2 years
Treatment resistance outcome 2
Time frame: From enrollment through 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2026.
- Background: PubMed 36230519Andersen LB, Mahler MSK, Andersen RF, Jensen LH, Raunkilde L. The Clinical Impact of Methylated Homeobox A9 ctDNA in Patients with Non-Resectable Biliary Tract Cancer Treated with Erlotinib and Bevacizumab. Cancers (Basel). 2022 Sep 22;14(19):4598. doi: 10.3390/cancers14194598.
- Background: PubMed 35251214Liu H, Yang H, Chen X. Prognostic Value of Circulating Tumour DNA in Asian Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2022 Feb 24;2022:8019652. doi: 10.1155/2022/8019652. eCollection 2022.
- Background: PubMed 34800650Guven DC, Sahin TK, Yildirim HC, Aktepe OH, Dizdar O, Yalcin S. A systematic review and meta-analysis of the association between circulating tumor DNA (ctDNA) and prognosis in pancreatic cancer. Crit Rev Oncol Hematol. 2021 Dec;168:103528. doi: 10.1016/j.critrevonc.2021.103528. Epub 2021 Nov 17.
- Background: PubMed 21266979Friend E, Yadegarfar G, Byrne C, Johnson CD, Sezer O, Pucciarelli S, Pereira SP, Chie WC, Banfield A, Ramage JK; EORTC Quality of Life Group. Development of a questionnaire (EORTC module) to measure quality of life in patients with cholangiocarcinoma and gallbladder cancer, the EORTC QLQ-BIL21. Br J Cancer. 2011 Feb 15;104(4):587-92. doi: 10.1038/sj.bjc.6606086. Epub 2011 Jan 25.
- Background: PubMed 8433390Aaronson 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.
- Background: PubMed 32154886Marschner N, Zacharias S, Lordick F, Hegewisch-Becker S, Martens U, Welt A, Hagen V, Gleiber W, Bohnet S, Kruggel L, Dille S, Nusch A, Dorfel S, Decker T, Janicke M. Association of Disease Progression With Health-Related Quality of Life Among Adults With Breast, Lung, Pancreatic, and Colorectal Cancer. JAMA Netw Open. 2020 Mar 2;3(3):e200643. doi: 10.1001/jamanetworkopen.2020.0643.
- Background: PubMed 20030832Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008. Health Qual Life Outcomes. 2009 Dec 23;7:102. doi: 10.1186/1477-7525-7-102.
- Background: PubMed 33857886Jakobsen A, Andersen RF, Hansen TF, Jensen LH, Faaborg L, Steffensen KD, Thomsen CB, Wen SWC. Early ctDNA response to chemotherapy. A potential surrogate marker for overall survival. Eur J Cancer. 2021 May;149:128-133. doi: 10.1016/j.ejca.2021.03.006. Epub 2021 Apr 12.
- Background: PubMed 28778958Spindler KG, Boysen AK, Pallisgard N, Johansen JS, Tabernero J, Sorensen MM, Jensen BV, Hansen TF, Sefrioui D, Andersen RF, Brandslund I, Jakobsen A. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2017 Sep;22(9):1049-1055. doi: 10.1634/theoncologist.2016-0178. Epub 2017 Aug 4.
- Background: PubMed 31109923Goyal L, Shi L, Liu LY, Fece de la Cruz F, Lennerz JK, Raghavan S, Leschiner I, Elagina L, Siravegna G, Ng RWS, Vu P, Patra KC, Saha SK, Uppot RN, Arellano R, Reyes S, Sagara T, Otsuki S, Nadres B, Shahzade HA, Dey-Guha I, Fetter IJ, Baiev I, Van Seventer EE, Murphy JE, Ferrone CR, Tanabe KK, Deshpande V, Harding JJ, Yaeger R, Kelley RK, Bardelli A, Iafrate AJ, Hahn WC, Benes CH, Ting DT, Hirai H, Getz G, Juric D, Zhu AX, Corcoran RB, Bardeesy N. TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma. Cancer Discov. 2019 Aug;9(8):1064-1079. doi: 10.1158/2159-8290.CD-19-0182. Epub 2019 May 20.
- Background: PubMed 36089135Berchuck JE, Facchinetti F, DiToro DF, Baiev I, Majeed U, Reyes S, Chen C, Zhang K, Sharman R, Uson Junior PLS, Maurer J, Shroff RT, Pritchard CC, Wu MJ, Catenacci DVT, Javle M, Friboulet L, Hollebecque A, Bardeesy N, Zhu AX, Lennerz JK, Tan B, Borad M, Parikh AR, Kiedrowski LA, Kelley RK, Mody K, Juric D, Goyal L. The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Ann Oncol. 2022 Dec;33(12):1269-1283. doi: 10.1016/j.annonc.2022.09.150. Epub 2022 Sep 9.
- Background: PubMed 34626563Kam AE, Masood A, Shroff RT. Current and emerging therapies for advanced biliary tract cancers. Lancet Gastroenterol Hepatol. 2021 Nov;6(11):956-969. doi: 10.1016/S2468-1253(21)00171-0.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared due to ethical, legal, and privacy considerations. The dataset contains sensitive clinical information, biomarker results (including ctDNA analyses), and patient-reported outcomes that could potentially allow re-identification of participants despite pseudonymization. Data collection and storage are governed by informed consent, data protection regulations, and regional legislation (e.g., GDPR), which restrict the sharing of identifiable or potentially identifiable health data beyond the approved research purposes. Additionally, the consent obtained specifies use of data within the scope of the study and related ethically approved research. Therefore, only aggregated and anonymized results will be reported in publications, and any future data sharing would require additional ethical approval and appropriate data-sharing agreements to ensure participant confidentiality and compliance with applicable regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohamed Metwally, Consultant, MD, PhD principal investigator
Aarhus University Hospital
Karen-Lise Garm Spindler, Professor, MD, PhD study chair
Aarhus University Hospital
Lise Thorsen, Associate professor, MD, PhD study chair
Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Biliary Tract Cancer (BTC) and Biliary Tract Cancer (CCA), run by Aarhus University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamed Metwally, MD, PhD (+4578454872, hassan@oncology.au.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (DFS) (time frame: From enrollment to the end of 5-years follow up period.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07454486, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2026.