Clinical trial NCT05704530: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Esophageal Cancer
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Kom Op Tegen Kanker
First posted: 2023-01-30
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: To assess the potency of ctDNA MRD variant allele frequency to improve clinical staging at diagnosis of esophageal cancer.
timeFrame: 12 months
measure: To correlate the presence of minimal residual disease after resection as assessed by ctDNA with disease recurrence.
timeFrame: 12 months
measure: To observe the ctDNA MRD dynamics during adjuvant immunotherapy .
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: UZA
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZLeuven
city: Roeselare
country: Belgium
facility: AZ Delta
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Jeroen Dekervel, MD
role: PRINCIPAL_INVESTIGATOR
References: