A Phase II Trial of Epirubicin, Oxaliplatin and Capecitabine (EOX) Versus Docetaxel and Oxaliplatin (ElTax) in the Treatment of Advanced Gastro-oesophageal Cancer

Study Overview
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Brief Summary
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Whilst oxaliplatin and docetaxel have established activity in the treatment of advanced gastro-oesophageal cancer, their role, however, in the management of this disease remains unclear. Furthermore it is unclear whether this disease is optimally treated with a combination of two or three cytotoxic drugs. This trial aims to determine whether the combination of oxaliplatin and weekly docetaxel warrants further investigation in a formal phase III trial. The combination of epirubicin, oxaliplatin and capecitabine will be the comparator arm for this evaluation. Primary Objective: Determine in a randomised study if the response rate to docetaxel and oxaliplatin (ElTax) is comparable to epirubicin, oxaliplatin and capecitabine (EOX) and warrants further evaluation in advanced gastro-oesophageal cancer. Secondary Objective: To examine the effect of treatment on time to progression, progression free survival, overall survival, quality of life, and the associated toxicity from treatment.

Detailed Description
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This is a randomised two-arm parallel group phase II study. 140 patients will be recruited over a period of 12 months, and will be randomised to receive either eight 3-weekly cycles of Epirubicin, Oxaliplatin and Capecitabine (EOX) or six 4-weekly cycles of Docetaxel and Oxaliplatin (EITax).

Official Title
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A Randomised Phase II Trial of Epirubicin, Oxaliplatin and Capecitabine (EOX) Versus Docetaxel and Oxaliplatin (ElTax) in the Treatment of Advanced Gastro-oesophageal Cancer

Conditions
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Gastro Oesophageal Cancer

Intervention / Treatment
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* Drug: Epirubicin
* Drug: Oxaliplatin
* Drug: Capecitabine
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable or metastatic, histologically confirmed adenocarcinoma of the stomach, gastro-oesophageal junction or lower third of the oesophagus with measurable disease on CT scanning (see RECIST Criteria, Appendix C of the protocol for definition of measureable disease). No previous treatment for advanced disease (previous adjuvant/neo-adjuvant treatment acceptable if >12 months previously). Absence of serious concomitant illness (i.e. MI within previous 6 months), uncontrolled angina, uncontrolled hypertension, severe COPD (>3 admissions for infective exacerbation in past 12 months) etc. ECOG performance status ≤ 2. Age ≥ to 18. Life expectancy ≥ 3 months Adequate renal, hepatic and bone marrow function Creatinine clearance ≥ 50 ml/min as calculated using the Cockcroft and Gault formula (see Appendix L). Liver function tests: Bilirubin ≤ 1.0 x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN,Haemoglobin > 10.0 g/dl, Absolute neutrophil count >1.5 x 109 /L, Platelet count > 100 x109/L. •Before randomisation, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion Criteria: Symptoms or signs of peripheral neuropathy. Patients known to have second or third degree heart block. Previous or concurrent malignancy, with the exception of basal cell carcinoma of the skin or in-situ neoplasia of the uterine cervix. Known hypersensitivity to taxanes, oxaliplatin, or fluoropyrimidines. Pregnant or nursing. Female of child-bearing potential, or male partner of female of child bearing potential not taking adequate contraceptive precautions. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epirubicin, Oxaliplatin, Capecitabine<br>Epirubicin 50mg/m2 (day 1) bolus injection Oxaliplatin 130mg/m2 (day 1) in 250mls of 5% dextrose. i.v. over 2 hours Capecitabine 625mg/m2 (days 1-21) b.d. orally 8 x 3-weekly cycle | Drug: Epirubicin<br> <br> Drug: Oxaliplatin<br> <br> Drug: Capecitabine<br> <br> |
| Active Comparator: Docetaxel, Oxaliplatin<br>Docetaxel 20mg/m2 (days 1, 8 & 15)in 250mls of 5% dextrose. i.v. over 30mins (Dexamethasone 8mg i.v, Chlorpheniramine 10mg i.v,Ranitidine 50mg i.v. to be given 30 minutes prior to Docetaxel) Oxaliplatin 85mg/m2 (days 1 & 15)in 250mls of 5% dextrose. i.v. over 2 hours 6 x 4-weekly cycle | Drug: Oxaliplatin<br> <br> Drug: Docetaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine in a randomised study if the response rate to docetaxel and oxaliplatin (ElTax) is comparable to epirubicin, oxaliplatin and capecitabine (EOX) and warrants further evaluation in advanced gastro-oesophageal cancer |  | Two Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In addition we will examine the effect of treatment on time to progression. |  | Two Years | 
| To examine the associated toxicity from treatment |  | 2 years | 
| To examine the effect of treatment on survival |  | 2 years | 
| To examine the effect of treatment on Quality of life. |  | 2 years |