Liquid Biopsies in Esophageal Cancer

• ClinicalTrials.gov Identifier: NCT05704530
• Recruitment Status: Recruiting
• First Posted: January 30, 2023
• Last Update Posted: April 10, 2023
• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborator: Kom Op Tegen Kanker
• Information provided by (Responsible Party): Universitaire Ziekenhuizen KU Leuven

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Esophageal Cancer	Other: Blood sample	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 248 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Three distinct patient groups are defined, depending on the therapeutic scenario patients undertake. Patient management is standard of care. No investigational medicinal product (IMP) is involved.

Trial is considered low interventional due to addition of extra blood samples, otherwise would be observational.

• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Personalized Multimodal Treatment for Resectable Esophageal Cancer by Detecting Minimal Residual Disease Using Circulating Tumor DNA: a Multicentric Prospective Study
• Actual Study Start Date: March 29, 2023
• Estimated Primary Completion Date: September 30, 2025
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm	Intervention/treatment
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.
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.
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.

Outcome Measures

Primary Outcome Measures :

1. To assess the potency of ctDNA MRD variant allele frequency to improve clinical staging at diagnosis of esophageal cancer. [ Time Frame: 12 months ]
   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.
2. To correlate the presence of minimal residual disease after resection as assessed by ctDNA with disease recurrence. [ Time Frame: 12 months ]
   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).
3. To observe the ctDNA MRD dynamics during adjuvant immunotherapy . [ Time Frame: 12 months ]
   To describe the dynamics of ctDNA concentration (proportion of clearance of positive ctDNA) during standard of care adjuvant immunotherapy.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Contacts

Contact: Jeroen Dekervel, MD; 016344225; jeroen.dekervel@uzleuven.be

Contact: Filip Van Herpe, MD; 016344225; filip.vanherpe@uzleuven.be

Locations

Belgium

UZA; Not yet recruiting

Antwerpen, Belgium

Principal Investigator: Timon Vandamme, MD

UZ Gent; Not yet recruiting

Gent, Belgium

Principal Investigator: Karen Geboes

UZLeuven; Recruiting

Leuven, Belgium

Contact: Filip Van Herpe, MD

Principal Investigator: Jeroen Dekervel, MD

AZ Delta; Recruiting

Roeselare, Belgium

Contact: Katleen Kerstens

Principal Investigator: Jochen Decaestecker, MD

Sponsors and Collaborators

Universitaire Ziekenhuizen KU Leuven

Kom Op Tegen Kanker

Investigators

• Principal Investigator: Jeroen Dekervel, MD; Universitaire Ziekenhuizen KU Leuven

More Information

• Responsible Party: Universitaire Ziekenhuizen KU Leuven
• ClinicalTrials.gov Identifier: NCT05704530
• Other Study ID Numbers: S67328
• First Posted: January 30, 2023
• Last Update Posted: April 10, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases