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
- Conditions
- Advanced oesophago-gastric cancerCancerOesophago-gastric cancer
- Registration Number
- ISRCTN65080435
- Lead Sponsor
- The Royal Marsden Hospital NHS Foundation Trust (UK)
- Brief Summary
2013 Results article in http://www.ncbi.nlm.nih.gov/pubmed/23594787 results
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 553
1. Male and female patients aged >=18 years, with no upper age limit
2. Histologically verified inoperable locally advanced or metastatic adenocarcinoma or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction, or stomach.
3. Slides of tumour tissue should be available for centralised EGFR staining
4. Uni-dimensionally measurable disease (computerised tomography [CT] or Magnetic resonance imaging [MRI] as per Response Evaluation Criteria In Solid Tumours [RECIST])
5. No prior chemotherapy including previous adjuvant chemotherapy
6. No prior radiotherapy including adjuvant radiotherapy
7. Wrold Health Organisation Performance status 0, 1 or 2
8. Patients should have a projected life expectancy of at least 3 months
9. Completion of baseline quality of life questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients [EORTC QLQ-C30])
10. Adequate cardiac function; formal measurement of left ventricular ejection fraction is only required if clinically indicated
11. Adequate bone marrow function: absolute neutrophil count (ANC) >=1.5 x 10^9/l; white blood cell count >=3 x 10^9/l; platelets >=100 x 10^9/l; haemoglobin (Hb) >=9 g/dl (can be post-transfusion)
12. Adequate renal function: calculated creatinine clearance >=50 ml/minute
13. Adequate liver function: serum bilirubin <=1.5 x upper limit of normal (ULN); ALT/AST <=2.5x ULN; alkaline phosphatase (ALP) <=3 x ULN (in the absence of liver metastases). If liver metastases are present, serum transaminases <= 5 x ULN are permitted.
14. Written informed consent must be obtained from the patient before any study-specific procedures are performed
1. Tumours of squamous histology
2. Patients with locally advanced oesophageal cancer suitable for definitive chemoradiotherapy.
3. Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease
4. Previous chemotherapy or radiotherapy
5. Any major surgery within 4 weeks prior to the start of study treatment
6. Any prior treatment with an epidermal growth factor receptor (EGFR) signal transduction directed therapy
7. Treatment with non-permitted medication
8. 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
9. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
10. Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
11. 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)
12. Known dihydropyrimidine dehydrogenase (DPD) deficiency
13. Known hypersensitivity to panitumumab, components of the EOX regimen, or any of the constituents of these agents
14. Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
15. Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial
16. 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
17. 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
18. 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)
19. Treatment with another investigational agent within 30 days of commencing study treatment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall survival (OS): The time between randomisation and death from any cause). Follow-up will be every 3 months until disease progression or death from any cause.
- Secondary Outcome Measures
Name Time Method <br> 1. Response rate (RR), measured according to the RECIST criteria<br> 2. Progression-free survival (PFS): The time between randomisation and disease progression (on CT or clinically)<br> 3. Toxicity, measured according to CTCAE version 3.0<br> 4. Quality of life, measured using the EORTC QLQ-C30 questionnaire, performed at baseline, prior to each cycle, then once during follow-up (3-months post treatment)<br> 5. The effect of K-ras mutation status on OS, RR and PFS<br> 6. Biomarkers (including K-ras mutation status and EGFR gene copy number) will be tested on the patients' diagnostic tumour sample<br><br> CT scans are planned at baseline, after 12 and 24 weeks, then to confirm clinically-apparent disease progression where appropriate.<br>