Liquid Biopsies in Esophageal Cancer

Personalized Multimodal Treatment for Resectable Esophageal Cancer by Detecting Minimal Residual Disease Using Circulating Tumor DNA: a Multicentric Prospective Study

Purpose of this study is to determine the value of liquid biopsies, e.g. testing of minimal residual disease (MRD) by using liquid biopsies to measure circulating tumour DNA (ctDNA) at diagnosis and during the multimodal and multidisciplinary curative-intent treatment of resectable esophageal cancer.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Other: Blood sample

Detailed Description

Multicentric, retrospective and prospective components.

Retrospective collection of leftover tissue from standard of care biopsies or resection specimens and prospective collection of additional blood samples for study-specific analyses at specific timepoints, at the same time as routine labs are foreseen. No additional venipunctures are expected.

Three distinct patient groups are defined, depending on the therapeutic scenario patients undertake:

Scenario 1: primary resection then follow-up - Study-specific liquid biopsies will be collected in 98 patients, at the time of routine labs. Samples will be acquired before resection, at 6-8 weeks, 6 and 12 months after resection.

Scenario 2: chemoradiation followed by resection and follow-up - Study-specific liquid biopsies will be collected in 50 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks, 6 and 12 months after surgery. A subgroup of patients will undertake adjuvant immunotherapy and will constitute Group 3. Timing of sampling will be adjusted accordingly as per study flowcharts.

Scenario 3: chemoradiation followed by resection followed by adjuvant immunotherapy - Study-specific liquid biopsies will be collected in 100 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks after surgery and during adjuvant immunotherapy every 3 months including a sample at the end of treatment.

Patient management is standard of care. No investigational medicinal product (IMP) is involved.

Specific clinicopathological variables will be collected in a RedCap electronic Case Report Form and analysed as per statistical analysis plan.

• Study Type: Interventional
• Enrollment (Estimated): 248
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeroen Dekervel, MD; Phone Number: 016344225; Email: jeroen.dekervel@uzleuven.be
• Study Contact Backup: Name: Filip Van Herpe, MD; Phone Number: 016344225; Email: filip.vanherpe@uzleuven.be

Study Locations

• Belgium
  • Antwerp, Belgium
    • Recruiting
    • UZA
    • Principal Investigator: Timon Vandamme, MD
  • Ghent, Belgium
    • Recruiting
    • UZ Gent
    • Principal Investigator: Karen Geboes
  • Leuven, Belgium
    • Recruiting
    • UZLeuven
    • Contact: Filip Van Herpe, MD
    • Principal Investigator: Jeroen Dekervel, MD
  • Roeselare, Belgium
    • Recruiting
    • AZ Delta
    • Contact: Katleen Kerstens
    • Principal Investigator: Jochen Decaestecker, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria are:

1. Male or female, age > 18 years
2. New diagnosis of esophageal cancer, pathologically confirmed squamous cell carcinoma (ESCC) or adenocarcinoma (EAC)
3. Clinically staged - cT1-4 N0-2 M0 (local or locally advanced, resectable)
4. Eligible for multidisciplinary treatment as assessed by MDT
5. Able to provide informed consent (ICF) according to Good Clinical Practice and national/European regulations

Key exclusion criteria are:

1. (Oligo)metastatic disease
2. Histologically or cytologically confirmed diagnosis other than squamous cell carcinoma or adenocarcinoma (eg. neuroendocrine carcinoma, lymphoma…)
3. Other active malignancies
4. Previous exposure to chemoradiation (prior to MDT)
5. Treatment plan after MDT: neoadjuvant chemotherapy with no radiation or chemoradiation with definitive intent (surgery is not planned)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1. primary resection then follow-up; Scenario 1: primary resection then follow-up - Study-specific liquid biopsies will be collected in 98 patients, at the time of routine labs. Samples will be acquired before resection, at 6-8 weeks, 6 and 12 months after resection.	Other: Blood sample; Retrospective collection of leftover tissue from standard of care biopsies or resection specimens and prospective collection of additional blood samples for study-specific analyses at specific timepoints, at the same time as routine labs are foreseen. No additional venipunctures are expected.
Other: 2. chemoradiation followed by resection and follow-up; Scenario 2: chemoradiation followed by resection and follow-up - Study-specific liquid biopsies will be collected in 50 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks, 6 and 12 months after surgery. A subgroup of patients will undertake adjuvant immunotherapy and will constitute Group 3. Timing of sampling will be adjusted accordingly as per study flowcharts.	Other: Blood sample; Retrospective collection of leftover tissue from standard of care biopsies or resection specimens and prospective collection of additional blood samples for study-specific analyses at specific timepoints, at the same time as routine labs are foreseen. No additional venipunctures are expected.
Other: 3. chemoradiation followed by resection followed by adjuvant immunotherapy; chemoradiation followed by resection followed by adjuvant immunotherapy - Study-specific liquid biopsies will be collected in 100 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks after surgery and during adjuvant immunotherapy every 3 months including a sample at the end of treatment.	Other: Blood sample; Retrospective collection of leftover tissue from standard of care biopsies or resection specimens and prospective collection of additional blood samples for study-specific analyses at specific timepoints, at the same time as routine labs are foreseen. No additional venipunctures are expected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the potency of ctDNA MRD variant allele frequency to improve clinical staging at diagnosis of esophageal cancer.	To assess whether ctDNA concentration can significantly contribute to preoperative staging in esophageal cancer, to define a significant cut-off value of ctDNA concentration with optimal sensitivity and specificity and validate the results.	12 months
To correlate the presence of minimal residual disease after resection as assessed by ctDNA with disease recurrence.	To compare the two groups ctDNA positive and negative post-resection in terms of progression-free survival and overall survival (Kaplan-Meier time-to-event) and evaluate the performance of ctDNA to predict disease recurrence (Cox proportional hazards model).	12 months
To observe the ctDNA MRD dynamics during adjuvant immunotherapy .	To describe the dynamics of ctDNA concentration (proportion of clearance of positive ctDNA) during standard of care adjuvant immunotherapy.	12 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Kom Op Tegen Kanker
• Investigators: Principal Investigator: Jeroen Dekervel, MD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: S67328

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No