An interventional study of NGS sequencing of mutations selected based on sequencing of primary tumors in Esophageal Adenocarcinoma, Gastric Cancer and Pancreatic Cancer, sponsored by Masaryk Memorial Cancer Institute. Recruiting at 1 site in Czechia. Per ClinicalTrials.gov, last updated 2026-06-24.
Sponsored by Masaryk Memorial Cancer Institute · Not applicable, Interventional, and Diagnostic
Preoperative neoadjuvant chemotherapy is the standard treatment for locally advanced gastrointestinal tumours. However, not all patients respond to preoperative treatment. Early identification of progression during neoadjuvant chemotherapy or diagnosis of early disease relapse during adjuvant treatment is essential to modify the treatment strategy. The aim of this project is to validate ctDNA as a biomarker of molecular relapse/progression of disease.
Neoadjuvant chemotherapy is the standard of care for locally advanced gastrointestinal tumors. However, not all patients respond to preoperative treatment. Early identification of disease progression during neoadjuvant chemotherapy or diagnosis of early disease relapse during adjuvant therapy is essential for modifying the treatment strategy. The aim of the project is to validate ctDNA as a molecular biomarker of disease relapse/progression.
The persistence of tumor cells after primary treatment of cancer is a key prognostic indicator of the disease's future course. In solid tumors, minimal residual disease (MRD) may involve tumor cells in the blood, small metastases in the body, or a small portion of the primary tumor that remains after treatment. Detection of MRD at a stage when the tumor cannot be detected by morphological imaging techniques is becoming an important diagnostic indicator that could better stratify patients after primary treatment in the future. MRD determination should thus serve in the future both to indicate further treatment and to monitor treatment response. For the successful clinical application of MRD determination, it is crucial to establish a sufficiently sensitive and specific method based on the detection of circulating tumor DNA (ctDNA). Tumor ctDNA is a component of circulating free DNA (cfDNA), which is released into the plasma from apoptotic or necrotic cells in the form of fragments with an average length of approximately 170 bp. The release of DNA from cells into the bloodstream can be influenced by a number of factors, which is reflected in the high variability of total cfDNA concentration, which can range from 1 to 100,000 fragments per milliliter of plasma. Therefore, to quantify MRD, it is crucial to determine both the total concentration of cfDNA and the proportion of tumor ctDNA. To reliably distinguish tumor ctDNA from non-tumor cfDNA, the detection of mutations identified in the primary tumor is currently used. For this purpose, PCR or digital PCR detecting specific mutations using fluorescent probes can be used. An alternative to PCR is mutation detection using next-generation sequencing (NGS), which allows for the detection of multiple different mutations in parallel. A disadvantage of MRD determination using commercial NGS kits designed for liquid biopsies is the high financial cost and the time-consuming preparation of sequencing libraries. We hypothesize that deep sequencing of cfDNA targeting mutations identified in the primary tumor can significantly increase both the specificity and sensitivity of MRD detection from liquid biopsies. Deep sequencing of 2-3 genomic regions with known mutations should enable the parallel detection of MRD in multiple patients while reducing the cost of this type of testing compared to commercially available options.
354 studies on the registry are indexed under Adenocarcinoma Of Esophagus; 81 are open to participants now.
This study's planned enrollment of 34 is below the median of 51 across 277 interventional studies indexed under Adenocarcinoma Of Esophagus.
Browse Adenocarcinoma Of Esophagus studies →Masaryk Memorial Cancer Institute is the lead sponsor of 15 studies on the registry; 10 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with locally advanced potentially resectable esophageal, gastric, or pancreatic cancer receiving neoadjuvant/perioperative treatment will undergo serial blood sampling for plasma isolation and circulating tumor DNA (ctDNA) analysis. Samples will be collected prior to initiation of neoadjuvant therapy, at the time of surgery, and subsequently at approximately 3-month intervals for 1-2 years after surgery or until disease progression. ctDNA analyses will be performed using a targeted next-generation sequencing (NGS) approach to evaluate longitudinal changes in tumor-specific genomic alterations and their association with treatment response and disease recurrence.
Diagnostic Test: NGS sequencing of mutations selected based on sequencing of primary tumors
Participants with esophageal, gastric, or pancreatic cancer receiving first-line palliative systemic therapy will undergo serial blood sampling for plasma isolation and ctDNA analysis. Samples will be collected prior to initiation of systemic treatment and subsequently at approximately 3-month intervals during first-line therapy. ctDNA analyses will be performed using the same targeted NGS methodology to assess longitudinal changes in tumor-specific genomic alterations during systemic treatment.
Diagnostic Test: NGS sequencing of mutations selected based on sequencing of primary tumors
Sequencing of the primary tumor will be performed on a MiSeq instrument using the Accel-Amplicon panel, which covers the most common mutations. For deep sequencing of ctDNA, 2-3 genomic regions carrying mutations in the primary tumor will be selected for the patient. For these regions, sets of universal primers will be designed to amplify the mutations most commonly found in solid tumors (RAS, BRAF, TP53, EGFR, APC, etc.). Another set of universal primers will contain a sequence for indexing individual samples, enabling the parallel sequencing of up to 96 samples simultaneously. The sequencing library will be analyzed on a NextSeq 500 instrument, which allows for up to 400 million reads in a single sequencing run. The sequencing results will then be correlated with the clinical course of the disease.
Sensitivity of targeted NGS assay for ctDNA mutation detection
Proportion of tumor-confirmed driver mutations detected in plasma cfDNA using the developed targeted NGS assay. Unit of Measure: Percentage (%)
Time frame: Through study completion, an average of 24 months.
Monitoring ctDNA levels
A secondary objective is to monitor ctDNA levels throughout the patient's treatment and to determine appropriate intervals for plasma collection after surgery and during adjuvant therapy.
Time frame: Through study completion, an average of 24 months.
Variant allele frequency (VAF) of detected driver mutations in cfDNA
Quantitative assessment of tumor-specific mutations detected in cfDNA using targeted NGS sequencing. Unit of Measure: Variant allele frequency (%)
Time frame: Through study completion, an average of 24 months.
Plan to share: Yes — IPD to be shared in pseudonymized form during the study. IPD to be published in anonymized form.
Supporting information: Clinical study report
Time frame: after study completion
Access criteria: During the study, data will be managed in pseudonymized form in a protected database environment, available only for study team. After completion of the study, the data will be fully anonymized for publication purposes. All publication outputs of the study will be carried out by a team of researchers led by the principal investigator. The submission of each publication is subject to the approval of the principal investigator. The results of this study may be published or presented at scientific meetings after approval by the PI and always after anonymization of the subjects' personal data in accordance with Act No. 101/2000 Coll., on the protection of personal data.
Data sharing details ↗ · www.mou.cz
No publications or documents are linked to this record.
Started Aug 2022 (actual). Primary completion is estimated for Dec 2026, 52 months after the start.
Of 27 interventional studies with no phase under Adenocarcinoma Of Esophagus, half reached primary completion within 52 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 70. This study's planned 52 months is close to that.
How these figures are worked out, and which studies are left out of them.
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Masaryk Memorial Cancer Institute