Esophageal Cancer
Conditions
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.
Interventions
OTHERBlood 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.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Kom Op Tegen Kanker
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the potency of ctDNA MRD variant allele frequency to improve clinical staging at diagnosis of esophageal cancer. | 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. | 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 . | 12 months | To describe the dynamics of ctDNA concentration (proportion of clearance of positive ctDNA) during standard of care adjuvant immunotherapy. |
Countries
Belgium
Contacts
CONTACTJeroen Dekervel, MD
CONTACTFilip Van Herpe, MD
PRINCIPAL_INVESTIGATORJeroen Dekervel, MD
Universitaire Ziekenhuizen KU Leuven
Outcome results
None listed