Surgically resectable oesophageal adenocarcinoma deemed suitable for surgery and neoadjuvant/adjuvant chemotherapy Cancer
Conditions
Interventions
The trial design will piggyback onto the participant's regular standard of care (SoC) treatment such as surgery and chemotherapy (i.e., the vaccine will be given without any changes or disturbances to
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological diagnosis of oesophageal or gastroesophageal junctional (types 1, 2 or 3) adenocarcinoma, deemed suitable for surgery with curative intent 2. Deemed suitable for oesophagectomy with curative intent by the relevant multidisciplinary team 3. Planned neoadjuvant and adjuvant treatment with FLOT chemotherapy 4. ECOG performance status of 0 or 1 5. Written informed consent obtained for Phase I/Phase II. 6. Age 18 years and above 7. Willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits, examinations, biopsies and follow-up. 8. Adequate normal organ and marrow function as defined below. 8.1. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted, except for the following laboratory parameters, which must be within the ranges specified, regardless of clinical significance: 8.2. Lab Test Value required: Haemoglobin (Hb): = 90 g/L 8.3. Neutrophil count: = 1.5 x 10^9/L 8.4. Platelet count: = 100 x 10^9/L 8.5. Serum creatinine, or Creatinine Clearance: = 1.5x Institutional Upper Limit of Normal (ULN), or = 40 mL/min (by Cockcroft-Gault formula) 8.6. AST or ALT, AST (SGOT)/ALT (SGPT): = 2.5 x institutional upper limit of normal 8.7. Alkaline phosphatase: = 2.5 x ULN 8.8. Serum bilirubin: = 1.5 x institutional ULN. This will not apply to subjects with documented Gilbert’s syndrome as evidenced by persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 21/02/2025: 1. Prior treatment in another clinical study with an investigational product within 4 weeks prior to Day 1 of the study; any respective adverse events must have resolved to Grade 1 or lower to be eligible. 2. Any contraindications to the FLOT chemotherapy or planned surgery 3. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with coeliac disease vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded 4. Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis) 5. History of allogeneic organ transplant 6. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s Correction 7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent 8. Known history of previous clinical diagnosis of tuberculosis 9. History of severe allergic reactions to any unknown allergens or any components of the study drugs. 10. Known dihydropyrimidine dehydrogenase (DPD) deficiency 11. Peripheral sensory neuropathy with functional impairment. 12. History of sarcoidosis/sarcoidosis syndrome. 13. Major surgical procedure (as defined by the Investigator) within 30 days prior to Day 1 or still recovering from prior surgery. 14. SARS-CoV2 vaccine (mRNA, subunit/viral vector or other) within 6 weeks of administration of first dose of study drug(s); or any live attenuated vaccine within 28 days of first dose of study drug(s). 15. Women who are breastfeeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). 16. Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the trial and for 6 months after the last dose of trial IMP (both male and female patients). Male participants must use condoms for the duration of the trial and for 6 months after the last dose of trial IMP. 17. Patients unable to commit to avoiding contact with young children or the severely immunocompromised for 5 days after each IMP dose* 18. Any condition that, in the clinical judgment of the treating physician, is likely to interfere with the evaluation of trial treatment, interpretation of subject safety or trial results, prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk. *Defined as follows: ‘Young children’ are individuals aged 0 to 12 years old who do not otherwise meet the criteria for ‘severely immunocompromised’. ‘Severely immunocompromised’ are those who meet any of the following criteria: 1. Active haematological malignancy (excluding monoclonal gammopathy of undetermined significance (MGUS), or those currently receiving treatment for a haematological malignancy and/or those within 1 year of bone marrow or stem cell transplant 2. Solid organ transplant(s) requir
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome(s) as of 03/03/2026: The safety and tolerability of ITOP1 measured using data collected in the Case Report Form (CRF) and medical notes of the incidence of serious adverse events (SAEs), the incidence of Grade 3 or higher AEs (graded according to CTCAE v5.0), the incidence of immune-related adverse events (irAE) and participant progression to surgical resection during the treatment period (week 0-14) and follow-up period (week 28-104) _____ Previous primary outcome(s): The safety and tolerability of ITOP1 measured using data collected in the Case Report Form (CRF) and medical notes of the incidence of serious adverse events (SAEs), the incidence of Grade 3 or higher AEs (graded according to CTCAE v5.0), the incidence of immune-related adverse events (irAE) and participant progression to surgical resection during the treatment period (week 12-26) and follow-up period (week 40-116) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcome(s) as of 03/03/2026: 1. Immunogenicity of ITOP1 will be measured using the tumoral and peripheral immune responses to ITOP1, and kinetics of the ITOP1 induced specific T cell response through sample analysis of the tumour sample from surgery resection in addition to the translational blood samples taken at various visits from Baseline to Week 104 2. Preliminary clinical efficacy of ITOP1 will be measured by recurrence-free survival (recurrence at any site by RECIST v1.1) at follow-up CT/MRI scans (Week 28-104), and overall survival measured from the time of surgery (Week 2 through to Week 104, and optional long-term Follow-up period) _____ Previous key secondary outcome(s): 1. Immunogenicity of ITOP1 will be measured using the tumoral and peripheral immune responses to ITOP1, and kinetics of the ITOP1 induced specific T cell response through sample analysis of the tumour sample from surgery resection in addition to the translational blood samples taken at various visits from Baseline to Week 116 2. Preliminary clinical efficacy of ITOP1 will be measured by recurrence-free survival (recurrence at any site by RECIST v1.1) at follow-up CT/MRI scans (Week 40-116), and overall survival measured from the time of surgery (Week 14 through to Week 116, and optional long-term Follow-up period) | — |
Countries
England, United Kingdom
Contacts
Public ContactOCTO VISTA Trial Team
Outcome results
None listed