Liquid Biopsies in Esophageal Cancer
Study Details
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 |
|---|---|---|
|
N/A |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: 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.
|
| Other: 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.
|
| Other: 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
- 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.
Eligibility Criteria
Criteria
Key inclusion criteria are:
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Male or female, age > 18 years
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New diagnosis of esophageal cancer, pathologically confirmed squamous cell carcinoma (ESCC) or adenocarcinoma (EAC)
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Clinically staged - cT1-4 N0-2 M0 (local or locally advanced, resectable)
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Eligible for multidisciplinary treatment as assessed by MDT
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Able to provide informed consent (ICF) according to Good Clinical Practice and national/European regulations
Key exclusion criteria are:
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(Oligo)metastatic disease
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Histologically or cytologically confirmed diagnosis other than squamous cell carcinoma or adenocarcinoma (eg. neuroendocrine carcinoma, lymphoma…)
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Other active malignancies
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Previous exposure to chemoradiation (prior to MDT)
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Treatment plan after MDT: neoadjuvant chemotherapy with no radiation or chemoradiation with definitive intent (surgery is not planned)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Kom Op Tegen Kanker
Investigators
- Principal Investigator: Jeroen Dekervel, MD, Universitaire Ziekenhuizen KU Leuven
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- S67328