Oesophageal adenocarcinoma Cancer
Conditions
Interventions
Eligible participants who have provided informed consent will be randomised to one of three study arms (2:2:1 [Arm A: B: C (control)] using minimisation stratified by disease stage [TNM] and disease s
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1. Age =18 to 50% (as determined by echocardiography) 10. Adequate respiratory function: participants with symptomatic lung disease should have a pulmonary function test with FEV1.0>65% predicted.
Exclusion criteria
Exclusion criteria: 1. Squamous, adenosquamous or other non-adenocarcinoma tumour histology 2. Advanced inoperable or metastatic oesophageal adenocarcinoma 3. Oesophageal adenocarcinoma T1N0 and T4b 4. Oesophageal adenocarcinoma T4a evaluated as not curatively resectable by the local MDT 5. Gastric carcinoma (according to UICC TNM732) 6. Prior chemotherapy for gastrointestinal cancer 7. Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months) 8. Clinically significant lung disease in the opinion of the investigator 9. Uncontrolled, in the opinion of the investigator, intercurrent physical or mental illness 10. Existing peripheral neuropathy greater than grade 1 11. Concurrent or within 5 years other primary malignancy, except cutaneous squamous cell carcinoma, basal cell carcinoma or cervical carcinoma in situ 12. Prior thorax or intraabdominal radiotherapy 13. Participation in another intervention trial with interference of chemotherapeutic or chemoradiotherapheutic intervention during the last 30 days prior to informed consent 14. Known allergy or hypersensitivity to any of the trial drugs including Dihydropyrimidine dehydrogenase (DPD) deficiency 15. Pregnant or breastfeeding participants, or those who are planning pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The feasibility of total neoadjuvant treatment for oesophageal adenocarcinoma compared to standard perioperative chemotherapy measured from Day 0 (randomisation) to the day of surgery. The primary endpoint is a binary endpoint called “treatment completion” and is either “yes” or “no”. It is defined differently in Arm A and Arm B. In Arm A patients need to complete six cycles of FLOT and have surgery. In Arm B, patients need to complete four cycles of FLOT and 90% of CROSS RT fractions and have surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Tolerability of TNT in comparison to standard care, measured using the following from day 0 to week 26: 1. Number of completed FLOT cycles 2. Dose of FLOT components administered 3. Number of CROSS chemotherapy cycles administered 4. Dose of CROSS chemotherapy components administered 5. Number of CROSS RT fractions completed 6. Completion of four cycles of neoadjuvant FLOT in Arms B & C 7. Completion of eight cycles of neoadjuvant FLOT in Arm A 8. Completion of five cycles of neoadjuvant CROSS in Arm B 9. Commencement of postoperative FLOT in Arm C 10. Completion of four cycles of postoperative FLOT in Arm C Toxicity of TNT in comparison to standard care, measured using the following from day 0 to week 26: 1. Number of adverse events 2. Grade severity of AEs according to CTCAE v6.0 Pathological response of TNT in comparison to standard care, measured using the following at weeks 30-38: 1. Histopathological response according to Mandard criteria 2. Complete histopathological response rate 3. ypT status 4. ypN status (and number of LNs examined) 5. R0 status Surgical outcomes following TNT in comparison to standard care, measured using the following from day of surgery to 90 days postoperative: 1. Clavien-Dindo Grade 2 or higher surgical complication (including anastomotic leak, pneumonia, respiratory failure, cardiac ischaemia/arrhythmia, thrombus, intra-abdominal sepsis/collection, chyle leak) 2. Unplanned return to theatre 3. Unplanned admission to critical care 4. Unplanned hospital re-admission 30- and 90-day surgical mortality rate 5. Duration of hospital admission after surgery 6. Death (day of surgery to 30 and 90 days postoperative) Quality of life following TNT in comparison to standard care measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire scores (EORTC QLQ) -C30, EORTC QLQ-OG25, EORTC QLQ-OES18 at the following timepoints: Week 0 (pre-treatment initiation, first cycle of | — |
Countries
England, Scotland, Wales
Contacts
Public ContactPatricia Burns
Outcome results
None listed