ctDNA Monitoring in Patients With HCC and mCRC
A Prospective Randomized Trial Assessing the Impact of ctDNA Testing in Patients After Liver Resection or Transplantation Due to Metastases From Colorectal Cancer or Hepatocellular Carcinoma (HCC) on Treatment Strategies and Long-term Survival"
2 other identifiers
interventional
300
1 country
1
Brief Summary
"Liquid biopsy" is a collective term that refers to the analysis of cancer-derived biomarkers isolated from the biological fluids of cancer patients. The analysis of these blood components can be used for early cancer detection, staging, prognosis, drug resistance monitoring, and minimal residual disease (MRD) monitoring. The "liquid biopsy" is based on the fact that cancer cells release their DNA into the bloodstream, known as ctDNA (circulating tumor DNA). A sample of the patient's peripheral blood is sufficient to test ctDNA. There have been many studies in the literature on the usefulness of liquid biopsy in the treatment of various malignancies, such as breast cancer, prostate cancer, and colorectal cancer. However, this has been a lack of prospectively obtained data analyzing the impact on the ctDNA assessment of the progression and recurrence of the primary disease or the type of treatment applied to improve long-term survival. The ctDNA test is not a widely recognized technology for assessing the progression of neoplastic disease. Aim of the study/research hypothesis: the aim of the project is to clinically validate the value of the ctDNA test as a tool for early diagnosis of recurrence, assessment of cancer progression, the prognosis of treatment effects, and monitoring of therapy in patients with primary liver HCC or colorectal cancer metastases. Description of the methodology: The main objective of the work will be achieved through the implementation of specific objectives: 1) Recruitment of 300 patients, including 100 patients with colorectal liver limited metastasis, 100 patients with hepatocellular carcinoma (HCC) and 100 patients in the control group who will be qualified for liver resection or transplantation, and in whom ctDNA level testing will not be tested. 2) Taking blood samples from the patients. The detection of ctDNA requires only the collection of 10 ml of the patient's blood and the collection of specimens from the tumor after resection. Blood will be collected before, one month, and 6 months after surgery during routine oncology check-ups. Tumor specimens will be taken from the backside table and sent for final histopathological examination. Control "follow-up" will take place for 18 months from the first ctDNA blood collection. Based on the collected material, genetic analysis will be performed. In the first stage, a tumor section taken during liver resection, and DNA from the patient's blood will be analyzed the molecular (genetic) signature of the patient's tumor will be determined and several genetic changes characteristic of the change will be selected. Thereafter, the presence of the selected genetic variants will be assessed qualitatively and quantitatively in the pre-operative blood sample and all subsequent post-operative blood samples. The investigators assume that in a blood sample taken 4 weeks after surgery, ctDNA should be undetectable or detected at a low level. In order to assess the change in the level of ctDNA in the postoperative period, a third examination will be performed - 6 months after the operation. Any level of detected ctDNA will be considered significant. Each increase in the level of the analyzed mutations will indicate the potential progression of the disease. The results of molecular analyzes will be correlated with the assessment of imaging tests and the level of tumor markers performed as part of routine oncological control. This is a prospective observational study with a defined study group. These are patients with colorectal cancer metastases limited to the liver, i.e. stage IV of the cancer process, or patients with hepatocellular carcinoma (HCC) qualified for radical surgery or liver transplantation. Patients in the control group (without ctDNA tests) will be treated in accordance with the best clinical knowledge and accepted international recommendations. The statistical analysis of the results will use the SAS (Statistical Analysis System) software, considering the Kaplan-Meier method, log-rank tests, Cox proportional hazards regression, and logistic regression. The investigators hypothesize that the use of ctDNA will enable the identification of early disease progression or will identify patients with the highest risk of recurrence. In addition, it will improve the supervision of diseases and enable possible modification of treatment in patients with stage IV colorectal cancer or patients after liver resection or transplantation for HCC. In the future, oncological prevention will consist in blood tests, which will enable early detection of even those cancers that show symptoms only at an advanced stage, which will potentially improve the effectiveness of treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jan 2025
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2025
CompletedFirst Submitted
Initial submission to the registry
May 9, 2025
CompletedFirst Posted
Study publicly available on registry
June 3, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2028
June 3, 2025
January 1, 2025
2.1 years
May 9, 2025
May 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Assessment of the clinical value of ctDNA level
Assessment of the ctDNA concentration one day before surgery.
One day before surgery - first day of enrollment
Assessment of the clinical value of ctDNA level
Assessment of the ctDNA concentration one month after surgery
From enrollment to 30 days after a surgery.
Assessment of the clinical value of ctDNA level
Assessment of the ctDNA concentration 6 months after surgery.
From enrollment to 6 months after a surgery.
Assessment of the mutational status of patient cancer
Determining the mutation status of the patient's cancer tissue by performing next-generation sequencing
From enrollment to 6 months after a surgery.
Assessment of the mutational status of patient cancer
Determining the mutation status of the patient's cancer by performing ddPCR reaction.
From enrollment to 6 months after a surgery.
Assessment of the mutational status of patient cancer 30 days after surgery
Determination of mutation status in plasma, 30 days after the patient's surgery by performing ddPCR reaction. This study aims to determine the rate of tumor recurrence.
From enrollment to 6 months after a surgery.
Assessment of the mutational status of patient cancer 6 months after surgery
Determination of mutation status in plasma, 6 months after the patient's surgery by performing ddPCR reaction. This study aims to determine the rate of tumor recurrence.
From enrollment to 6 months after a surgery.
Secondary Outcomes (2)
Assessment of quality of life
From enrollment to 4 years after a surgery.
Comparative evaluation of imaging results with molecular results
From enrollment to 4 years after a surgery.
Study Arms (4)
Study Group - Colorectal Cancer with Liver Metastases
OTHERPatients with metastatic colorectal cancer to the liver. Tumor tissue obtained during surgery is subjected to DNA extraction and Next-Generation Sequencing (NGS) to identify oncogenic mutations. Blood samples are collected one day before surgery, one month, and six months after surgery. Plasma is separated from blood to isolate circulating tumor DNA (ctDNA), which is then tested using droplet digital PCR (ddPCR) to detect the mutations previously identified by NGS.
Study Group - Hepatocellular Carcinoma
OTHERPatients with hepatocellular carcinoma. Tumor tissue collected during surgery is analyzed using NGS to identify oncogenic mutations. Blood samples are collected at the same three time points. Plasma-derived ctDNA is tested using ddPCR for the previously detected mutations.
Control Group - Colorectal Cancer with Liver Metastases
OTHERPatients with metastatic colorectal cancer to the liver meeting control group criteria. Blood samples are collected one day before surgery, one month, and six months after surgery. Plasma is separated and stored, but no NGS or ddPCR analyses are performed.
Control Group - Hepatocellular Carcinoma
OTHERPatients with hepatocellular carcinoma meeting control group criteria. Blood is collected at three predefined time points. Plasma is separated and stored. No molecular or genetic testing is conducted on these samples.
Interventions
Tumor tissue is collected during surgery and used for DNA extraction. Next-Generation Sequencing (NGS) is performed to identify oncogenic mutations.
Blood is collected at three time points: one day before surgery, one month, and six months after surgery. Plasma is separated and used for further molecular analysis or storage.
Circulating tumor DNA (ctDNA) is isolated from plasma samples. Mutations previously identified by NGS are quantitatively analyzed using droplet digital PCR (ddPCR).
Eligibility Criteria
You may qualify if:
- age 18-75 years of both sexes;
- patients with synchronous or metachronous metastases of colorectal cancer limited to the liver after complete removal of the primary lesion from the intestine qualified for liver resection or transplantation;
- or patients with resectable or unresectable HCC scheduled for liver resection or transplantation
- no history of other cancers;
- negative virological status in the case of mCRC;
- In the case of mCRC - patient after any type of liver surgery (staged, ALPPS, multi-site resection)
- Patient with or without neoadjuvant chemotherapy compatible with established adjuvant therapy
You may not qualify if:
- age under 18 and over 75;
- pregnancy
- patients with extrahepatic metastases visible in imaging studies;
- metabolic and autoimmune diseases or chronic immunosuppressive treatment other than in the group of patients after liver transplantation due to HCC;
- positive virological status, excluding the group of patients with HCC;
- history of other cancer;
- Chronic steroid therapy and diagnosed active autoimmune diseases
- Patient after radiotherapy
- Patient participating in other clinical trials of oncological and non-oncological drugs
- Patients legally incapacitated
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical University of Warsawlead
- Medical Research Agency, Polandcollaborator
Study Sites (1)
Medical University of Warsaw
Warsaw, Masovian Voivodeship, 02-091, Poland
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tomasz Stokłosa, Professor
tomasz.stoklosa@wum.edu.pl
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- HEALTH SERVICES RESEARCH
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor, MD, PhD Oskar Kornasiewicz
Study Record Dates
First Submitted
May 9, 2025
First Posted
June 3, 2025
Study Start
January 1, 2025
Primary Completion (Estimated)
February 1, 2027
Study Completion (Estimated)
April 30, 2028
Last Updated
June 3, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR