Liquid Biopsies in Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05704530
• Other study ID #: S67328
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Jeroen Dekervel, MD
• Phone: 016344225
• Email: jeroen.dekervel[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Belgium	UZA	Antwerpen
Belgium	UZ Gent	Gent
Belgium	UZLeuven	Leuven
Belgium	AZ Delta	Roeselare

Sponsors (2)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	Kom Op Tegen Kanker

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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