Adenocarcinoma - Gastroesophageal Junction (GEJ), Gastric Adenocarcinoma, Gastroesophageal Junction (GEJ) Adenocarcinoma
Conditions
Keywords
oesophago-gastric adenocarcinoma, FDG-PET, metabolic response, preoperative treatment, response-adapted treatment
Brief summary
GastroPET is a prospective, multicenter, non-randomized interventional study evaluating sequential FDG-PET as an early biomarker to guide preoperative treatment in patients with locally advanced resectable oesophago-gastric adenocarcinoma. All patients receive an initial cycle of standard preoperative chemotherapy followed by a second FDG-PET scan. Based on the change in tumor FDG uptake, patients are classified as metabolic responders or non-responders. Metabolic responders continue preoperative chemotherapy, whereas metabolic non-responders switch to preoperative chemoradiotherapy. The study evaluates surgical and long-term outcomes of this response-adapted treatment strategy. Exploratory objectives include the evaluation of tissue and circulating miRNA and immune biomarkers in relation to metabolic response and treatment outcomes.
Detailed description
The primary objective of the study is to evaluate sequential FDG-PET as an early biomarker for response-adapted preoperative treatment in locally advanced resectable oesophago-gastric adenocarcinoma. FDG-PET is performed before initiation of preoperative chemotherapy and after the first cycle of chemotherapy. The change in tumor standardized uptake value (SUV) is used to classify patients as metabolic responders (Arm A) or metabolic non-responders (Arm B). Metabolic responders continue preoperative FLOT or FOLFOX chemotherapy, whereas metabolic non-responders switch to preoperative chemoradiotherapy with paclitaxel and carboplatin. The primary efficacy outcome is the R0 resection rate in Arm B. Secondary clinical outcomes include disease-free survival and overall survival in both metabolic response groups. Additional exploratory objectives include the evaluation of tissue and plasma miRNA profiles as biomarkers of metabolic and pathological response, assessment of circulating immune cells and antibody profiles in relation to metabolic response and treatment outcomes, and a pharmacokinetic substudy evaluating interpatient variability in fluoropyrimidine exposure and its association with adverse drug reactions.
Interventions
DIAGNOSTIC_TESTFDG-PET
FDG-PET scans will be performed before (baseline) and after 14 days of standard neoadjuvant treatment in specialized PET centers (MOÚ Brno, VFN Praha, FN Olomouc) according to the standard operation procedure and in accordance with the EANM guidelines. Data and records of the FDG-PET scans will be sent for central reading to PET Center MOÚ. Tracer uptake will be assessed semiquantitatively (standardized uptake values (SUV) using a circular region of interest (ROI) (diameter, 1.5 cm) with the TrueD software (Siemens Medical Solutions)). The percentage change in SUV will be calculated as ΔSUV = 100 × (SUVbaseline - SUVfollow-up)/SUVbaseline and used to classify patients as metabolic responders or non-responders and guide subsequent preoperative treatment.
Sponsors
Masaryk Memorial Cancer Institute
University Hospital Olomouc
General University Hospital, Prague
Masaryk University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
The main objective is to use sequential FDG-PET/CT scans as an early biomarker. After the initial PET scan, all patients undergo one cycle of standard neoadjuvant chemotherapy. Exactly 14 days after this cycle, a second PET scan is performed, and its results (a decrease in SUV of ≥35% or \<35%) will determine assignment to one of two treatment arms. The study is classified as an interventional study, even though it does not use any investigational (experimental) drug. The intervention consists of modifying the treatment algorithm based on the PET scan results, whereby non-responders immediately switch from ineffective chemotherapy to preoperative chemoradiotherapy. All treatments administered (FLOT, FOLFOX, or chemoradiotherapy with paclitaxel and carboplatin) are in line with standard clinical practice according to international ESMO and NCCN guidelines.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age of 18 years or more 2. Not currently participating in another study 3. Able and willing to sign informed consent and to comply with study procedures 4. Biopsy-proven locally advanced resectable oesophago-gastric adenocarcinoma (Siewert I - III) with T3N0, T4N0, T2 - T4N+, stage Ib - IIIc I. Adenocarcinoma of distal part of the oesophagus II. Adenocarcinoma of the real cardia III. Adenocarcinoma of the subcardial stomach 5. Staging procedures include endoscopy, endoscopic ultrasound and FDG-PET 6. Eligible patients have to be fit for platinum-containing chemotherapy 7. Tumours must be potentially R0 resectable tumours during consecutive operation.
Exclusion criteria
1. Participation in another clinical trial of a therapeutic drug during the past 14 days 2. Addiction to alcohol or drugs 3. Women of child-bearing potential who are not using a commonly accepted effective means of contraception; women of child-bearing potential will have negative blood pregnancy test before enrollment 4. Pregnant women and nursing mothers are not allowed to enroll on this study 5. Eastern Cooperative Oncology Group score \>2 6. Previous or secondary malignancy in past 5 years (Excluding skin cancer and early cervical carcinoma) 7. Life expectancy of less than 3 months 8. Uncontrolled bleeding from the tumour 9. Uncontrolled diabetes 10. Patients are also ineligible if they have undergone previous chemotherapy, radiotherapy, or endoscopic laser therapy for EGJ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate in arm B (metabolic non-responders) | At surgery, following completion of preoperative treatment | The proportion of patients in Arm B (metabolic non-responders) who achieve an R0 resection. Metabolic non-response is defined as a decrease in tumor standardized uptake value (SUV) of \<35% on FDG-PET performed after the first cycle of preoperative chemotherapy compared with baseline FDG-PET. R0 resection is defined as curative surgical resection with negative resection margins. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival in arm A and arm B | From the second FDG-PET scan until death from any cause, assessed up to 5 years | Overall survival (OS) is defined as the time from the second FDG-PET scan to death from any cause. OS will be evaluated in Arm A (metabolic responders) and Arm B (metabolic non-responders). |
| Disease free survival in arm A and arm B | From curative-intent resection (R0/R1) until disease recurrence or death from any cause, assessed up to 5 years | Disease-free survival (DFS) is defined as the time from curative-intent resection (R0/R1) to disease recurrence or death from any cause. DFS will be evaluated separately in Arm A (metabolic responders) and Arm B (metabolic non-responders). |
Countries
Czechia
Contacts
STUDY_CHAIRRegina Demlová, MD, PhD
demlova@mou.cz
Outcome results
None listed