REAL 3 : A Randomised Open-labelled Multicentre Trial of the Efficacy of Epirubicin, Oxaliplatin and Capecitabine (EOX) With or Without Panitumumab in Previously Untreated Advanced Oesophago-gastric Cancer
- Histologically verified inoperable locally advanced or metastatic adenocarcinoma or
undifferentiated carcinoma of the oesophagus, oesophago-gastric junction, or stomach.
- Slides of tumour tissue should be available for centralised EGFR staining
- Uni-dimensionally measurable disease (CT or MRI as per RECIST).
- No prior chemotherapy including previous adjuvant chemotherapy
- No prior radiotherapy including adjuvant radiotherapy. Patients receiving palliative
radiotherapy to sites of disease that are not measurable may be eligible and should
be discussed with the Chief Investigator.
- Male/female patients aged ≥18 years.
- WHO Performance status 0, 1 or 2.
- Patients should have a projected life expectancy of at least 3 months.
- Completion of baseline quality of life questionnaire (EORTC QLQ C30).
- Adequate cardiac function; formal measurement of left ventricular ejection fraction
is only required if clinically indicated.
- Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5x109/l; white
blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be
- Adequate renal function: calculated creatinine clearance ≥50ml/minute.
- Adequate liver function: serum bilirubin ≤1.5x ULN; ALT/AST ≤2.5x ULN; ALP ≤3x ULN
(in the absence of liver metastases). If liver metastases are present, serum
transaminases ≤5x ULN are permitted.
- Written informed consent must be obtained from the patient before any study-specific
procedures are performed (see Section 12.0).
Note: Epidermal growth factor receptor (EGFR) positivity by immunohistochemistry will not
be required for study entry. Slides obtained from previously collected paraffin embedded
archived specimens will be collected centrally for EGFR staining. A multivariate analysis
will then be performed to exclude any effects of EGFR status on outcome measures
- Tumours of squamous histology.
- Patients with locally advanced oesophageal cancer suitable for definitive
- Documented or symptomatic brain metastases and/or central nervous system metastases
or leptomeningeal disease.
- Previous chemotherapy or radiotherapy. See Inclusion criteria for note regarding
- Any major surgery within 4 weeks prior to the start of study treatment.
- Any prior treatment with an EGFR signal transduction directed therapy.
- Treatment with non-permitted medication.
- Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery
disease, uncontrolled cardiac dysrhythmia, or myocardial infarction within the last
12 months. Patients with any history of clinically significant cardiac failure are
excluded from study entry.
- History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or
evidence of interstitial lung disease on baseline chest CT scan.
- Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole
neurological abnormality does not render the patient ineligible).
- Lack of physical integrity of the upper gastro-intestinal tract, malabsorption
syndrome, or inability to take oral medication (administration of capecitabine by
naso-gastric or jejunostomy feeding tube is permitted).
- Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Known hypersensitivity to panitumumab, components of the EOX regimen, or any of the
constituents of these agents.
- Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C
virus, acute or chronic active hepatitis B infection.
- Other clinically significant disease or co-morbidity which may adversely affect the
safe delivery of treatment within this trial.
- Female patients who may be pregnant or breastfeeding. Potential female patients of
childbearing potential must have a negative pregnancy test within 7 days prior to
randomisation, or have had amenorrhea for more than 2 years.
- Patients of child-bearing potential not consenting to use adequate contraceptive
precautions or abstinence during the course of the study and for 6 months after the
last study drug administration for females, and 1 month for males.
- Any other malignancies within the last 5 years (other than curatively treated basal
cell carcinoma of the skin and/or in situ carcinoma of the cervix).
- Treatment with another investigational agent within 30 days of commencing study