Adenocarcinoma - GEJ, Barrett Esophagus, Barrett Esophagus Adenocarcinoma, Gastroenterological Cancer, Gastroenterology
Conditions
Keywords
Barrett Esophagus, Barrett, DNA FISH, Genetic profiling, Adenocarcinoma, Brush cytology, Cancer worry, Disease free survival, Randomized controlled trial, RCT, Endoscopic mucosal resection, Endoscopic submucosal dissection, EMR, ESD, Quality of life, Health-Economic analysis
Brief summary
The goal of the study is: * The collection of various tissue samples (blood, biopsies and "esophageal brushes") and their analysis. * To test a risk model based on genetic analyses (DNA-FISH and so-called single cell sequencing) on esophageal tissue samples. * Evaluating the quality of life of Barrett's Esophagus patients and the degree of fear of getting cancer. Patients with a Barrett's Esophagus can participate in the study if they are minimally 18 years old, are capable of giving informed consent (fully understanding what the study entails before giving consent to participate), have Barrett Esophagus and are referred to one of the participating centers due to suspicion of early esophageal cancer, for which the participant will be evaluated by endoscopic imaging and biopsy. Study procedures: An intake consultation will be planned, wherein the eligibility criteria will be assessed, and participant characteristics will be collected. A routine gastroscopy will be planned twice during which several minimally-invasive interventions will be performed: drawing a blood sample, brush cytology during the endoscopy (a brush is used to obtain cells from the surface of the esophagus) and obtaining biopsy samples (small pieces of tissue). Each participant will need to undergo all the interventions. Patients will have to complete questionnaires at several time points to assess their quality of life (EQ-5D-DL questionnaire) and fear of cancer recurrence (Cancer Worry Scale). This study is a randomized trial, meaning the study participants will be divided into two groups by the computer. One group will be informed of their risk profile, established based on the genetic analyses. The other group will not be informed of their risk profile. All patients will be followed-up in a more intensive surveillance schedule compared to the standard of care, for study purposes.
Detailed description
More specifically, you will have a standard endoscopy twice during which tissue samples will be taken from the esophagus to check for the severity of the disease. This is part of standard care. If you participate in the study, additional samples will be taken from the esophagus and also from the stomach (a total maximum of 10 samples of 1-2 mm). As a result, the endoscopic examination will take about 10-15 minutes longer than standard. Furthermore, in addition to the tissue samples, cells of the esophageal mucosa will be sampled (through 4 "esophageal brushes") and blood (up to 4 tubes) will also be collected. For this study, you will be contacted a total of four times. Once for a screening visit and twice for the sample collection described above. One last visite will be planned to discuss the risk profile, depending on the randomization group. After your initial treatment, you will be enrolled in a standard-of-care treatment schedule depending on your specific circumstances. This standard-of-care treatment schedule will coincide with the intensified surveillance schedule to detect recurrence earlier. Patient outcomes will be documented for the study until a maximum of 5 years after inclusion. This documentation will take place during the routine follow up so does not require any additional visits for the patients. Additionally you will be asked to complete two short questionnaires on your mobile phone at several time points during the study.
Interventions
OTHERRisk profile disclosure
Participants in the intervention arm will be informed by the investigator on their genetic risk profile.
Sponsors
University Hospital, Antwerp
Karolinska Institutet
Karolinska University Hospital
Amsterdam UMC
Radbound University Medical Center
University of Leipzig
IRCCS Ospedale San Raffaele
University of Dublin, Trinity College
St. James's Hospital, Ireland
Heinrich-Heine University, Duesseldorf
Rigshospitalet, Denmark
Universitätsklinikum Leipzig
GZA Ziekenhuizen Campus Sint-Augustinus
AZ Delta
Lille University Hospital
University Hospital, Ghent
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Masking description
In this trial, there will be two arms: * Control group = dubbel blind (investigator and patient are blinded for the results of the risk profile). * Intervention group = open label = patients will be informed by the investigator on their risk profile.
Intervention model description
RCT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with known BE undergoing endoscopy for possible treatment by EMR or ESD due to suspicion of T1 oesophageal Barrett cancer * Capable of receiving informed consent and of giving permission * Age 18 and upward
Exclusion criteria
* Patients with current known malignancy of the gastrointestinal tract other than the esophageal lesion * Patients refusing randomization and corresponding follow-up intervals based on biomarker profile * Patients with severe co-morbidity that prohibits endoscopic therapy under sedation or conscious sedation (such as severe cardiac or pulmonary disease) * Esophageal varices * Uncontrollable coagulation disorders * Undergoing/planned chemotherapy or immunotherapy or received chemotherapy \< 6 months prior to endoscopy * Undergoing/planned radiotherapy within the esophageal region or received radiotherapy \< 6 months prior to endoscopy * WHO score \>3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease recurrence | From endoscopic resection up to three years after endoscopic eradication therapy | Extraluminal recurrence (regional, distal) of cancer, endoluminal recurrence (metachronous, local) of cancer, endoluminal recurrence of dysplasia |
| Cancer Worry Scale | After cessation of endoscopic eradication therapy (EET), assessed up to 5 years after inclusion | Cancer Worry Scale (total score, 8-item version) after cessation of endoscopic eradication therapy (EET) |
| Economic costs | From end of endoscopic eradication therapy until three years after endocsopic eradication therapy | Economic costs in euro for surveillance programme (including endoscopic procedures, biomarker analysis and materials) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clonal diversity score | Between the baseline endoscopy (visit 1) and first endoscopy after endoscopic resection (visit 2) | Clonal diversity score measurements based on DNA-FISH brush cytology samples before and after endoscopic resection |
| Disease stage | From patient inclusion until three years after endoscopic eradication therapy | Disease stage (histopathological disease stage of resection specimen, TNM-classification) based on EMR/ESD, EUS, PET-CT, pathology and cytology |
| Missing data ePRO | From start of inclusion until three years after endoscopic eradication | Missing data events for ePRO and paper questionnaires |
| Caregiver's satisfaction | From start inclusion until three years after endoscopic eradication | Caregiver's responses to questionnaire on application of biomarker-based health information |
| Drop-out | From start inclusion until three years after endoscopic eradication | Drop-out/delay events from allocated endoscopic surveillance, reasons for delays/drop-out |
| Follow-up years | From end of endoscopic eradication therapy until year three after endoscopic eradication | Total follow-up years: mean and average follow-up years per patient |
| Cancer worry scale longitudinal | From start of inclusion until year three after endscopic eradication therapy | Cancer worry scale total score at predetermined, clinically relevant timepoints |
| EQ-5D-5L | From start of inclusion until three years after endoscopic eradication | EQ-5D-5L utility score and Visual Analogue Scale score at predetermined, clinically relevant timepoints |
| Quality adjusted life years (QALY) | From start of inclusion until three years after endoscopic eradication | QALY based on clinical endpoints, cancer worry scale results and EQ-5D-5L results |
| Endoscopy timepoint | From end of endoscopic resection until three years after endoscopic eradication therapy | Endoscopy timepoint at detected recurrence |
| Histopathological disease stage | From end of endoscopic resection until three years after endoscopic eradication | Histopathological disease stage of detected recurrence |
| Treatment stage recurrence | From endoscopic resection until three years after endocopic eradication | Treatment stage of detected recurrence (before / during / after RFA) |
| Mortality events | From endoscopic resection until three years after endoscopic eradication | Overall and disease-specific mortality events |
| Number of ablation sessions | From start of endoscopic eradication therapy until end of endoscopic eradication, assessed up to 5 years after inclusion | Amount of ablation sessions needed to achieve CE-IM |
| Number of CE-IM patients | From start of endoscopic eradication therapy until end of endoscopic eradication, assessed up to 5 years after inclusion | Number of patients that reach CE-IM |
| Number of RFA therapy-resistant patients | From start of endoscopic eradication therapy until end of endoscopic eradication, assessed up to 5 years after inclusion | Number of RFA therapy-resistant patients defined as \>50% residual Barrett Esophagus after first RFA session, or when residual BE is present after cessation of RFA therapy |
| Local recurrence | From endoscopic resection until three years after endoscopic eradication | Local recurrence of adenocarcinoma (around the EMR/ESD scar site) |
Countries
Belgium, Denmark, France, Germany, Ireland, Italy, Sweden
Contacts
CONTACTMartin Wyckmans, Resident Physician
CONTACTLuka Van der Veken, Master Biomedical Sciences
Outcome results
None listed