Peri-operative Immuno-Chemotherapy in Operable oesophageal aNd gastrIc Cancer

Phase 1

• Conditions: Operable oesophageal and gastric cancer; MedDRA version: 19.1 Level: PT Classification code 10062878 Term: Gastrooesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003306-13-GB
• Lead Sponsor: The Royal Marsden NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-23
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 53

Inclusion Criteria

i.Histologically confirmed gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (referred to as gastro-oesophageal adenocarcinoma (GOA) in this protocol).
ii.Oesophageal and gastric tumours should be TNM7 stage T1-3 and N0-N2, with no evidence of distant metastases (M0) where the MDT believes that an R0 resection can be achieved at the outset. T4 tumours will be excluded due to the variable need to prolong pre-operative chemotherapy or chemo-radiotherapy as part of locally advanced protocol to reduce margin involvement and improve resectability.
iii.Absence of distant metastases on CT scan and PET scan and staging laparoscopy (where indicated) prior to study entry
iv.No prior therapy for GOA
v.Adequate cardio-pulmonary reserve as assessed by: Supervised Incremental Shuttle Walk threshold > 350 metres, or formal CPET testing with an anaerobic threshold =9 mls/min/kg.
vi.Adequate bone marrow function:
•Absolute neutrophil count (ANC) >1.5x10-9/L
•White blood count >3x10-9/L
•Platelets =100x10-9/L
•Haemoglobin (Hb) >9g/dl (can be post-transfusion)
viii.Adequate renal function: glomerular filtration rate (GFR) =30ml/min calculated (as per local practice) or measured. If the calculated GFR is <60ml/min then a measured GFR is required. The measured GFR should always take precedence over the calculated GFR
ix.Adequate liver function
•Serum bilirubin =1.5x ULN
•ALT/AST =2.5x ULN
x.Adequate coagulation profile
•International Normalised Ratio (INR) < 1.5
•Activated Prothrombin Time (APTT) < 1.5xULN
xi.Patients on oral anticoagulation are advised to change to low molecular weight heparin prior to study entry, to be eligible
xii.ECOG performance status 0 or 1
xiii.BMI =35
xiv.Patient is fit to undergo all protocol investigations and receive all protocol treatment based on the assessment in the surgical and oncology clinics
xv.Male/female patients aged =18 years
xvi.Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment.
xvii.Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

Patients are not eligible for the trial if any of the exclusion criteria below are met:
i.Any contraindication or known hypersensitivity reaction to any of the study drugs, or components of Folinic acid, Oxaliplatin, or 5FU
ii.Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma)
iii.Known dihydropyrimidine dehydrogenase (DPD) deficiency
iv.Patients who have received chemotherapy, radiotherapy or immunotherapy for a previous malignancy
v.Any previous malignancy, with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
vi.Patients recommended to have radiotherapy as part of routine management for their GOA are ineligible
vii.Any immunodeficiency disorder
viii.Any active, known or suspected autoimmune disease that might deteriorate when receiving immunostimulatory agent, with the following exceptions:
•Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
•Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses =10mg (or equivalent) of prednisolone per day
•Administration of steroids through a route known to result in minimal systemic exposure (topical, intranasal intra-ocular, or inhalation) are acceptable
ix.Prior organ transplantation, including allogeneic stem-cell transplantation
x.History of inflammatory bowel disease
xi.Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis
xii.Cerebrovascular disease (including transient ischaemic attacks (TIA) and strokes) within the previous year
xiii.Cardiovascular diseases as follows:
•Myocardial infarction within the previous year
•Serious cardiac arrhythmia requiring medication (for example,
ventricular tachycardia, supraventricular tachycardia or atrial fibrillation with a resting heart rate > 110bpm)
xiv.Current signs or symptoms of any other severe progressive or uncontrolled hepatic, haematologic, gastrointestinal, endocrine, respiratory or cardiac disease other than directly related to gastro-oesophageal adenocarcinoma, which in the opinion of the investigator, might impair the subject’s tolerance of trial treatment or procedures.
xv.Major surgery, major trauma or open biopsy within 28 days prior to registration (not including staging laparoscopy)
xvi.Evidence of bleeding diathesis or coagulopathy
xvii.Active non-healing wound, ulcer or bone fracture requiring therapy
xviii.Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis A or C virus, acute or chronic active hepatitis B infection
xix.Known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
xx.Use of live attenuated vaccine within 28 days of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified