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

Tracking Information

• First Submitted Date: January 19, 2023
• First Posted Date: January 30, 2023
• Last Update Posted Date: April 10, 2023
• Actual Study Start Date: March 29, 2023
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2023)

• 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.
• 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).
• 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Liquid Biopsies in Esophageal Cancer
• Official Title: Personalized Multimodal Treatment for Resectable Esophageal Cancer by Detecting Minimal Residual Disease Using Circulating Tumor DNA: a Multicentric Prospective Study
• 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.

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
• Study Phase: Not Applicable

Study Design

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

• Condition: Esophageal Cancer

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.

Study Arms

• 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.
  Intervention: Other: Blood sample
• 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.
  Intervention: Other: Blood sample
• 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.
  Intervention: Other: Blood sample

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 19, 2023): 248
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT05704530
• Other Study ID Numbers: S67328
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Universitaire Ziekenhuizen KU Leuven
• Original Responsible Party: Same as current
• Current Study Sponsor: Universitaire Ziekenhuizen KU Leuven
• Original Study Sponsor: Same as current
• Collaborators: Kom Op Tegen Kanker

Investigators

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

• PRS Account: Universitaire Ziekenhuizen KU Leuven
• Verification Date: March 2023