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

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

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.

Study Overview

• Status: Completed
• Conditions: Gastro Oesophageal Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Epirubicin; Drug: Oxaliplatin; Drug: Capecitabine

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Cork, Ireland
    • Mercy University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • St James's Hospital
  • Dublin, Ireland
    • The Adelaide and Meath Hospital
  • Dublin, Ireland
    • Mater Misericordiae University Hospital & Mater Private Hospital
  • Waterford, Ireland
    • Waterford Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Epirubicin, Oxaliplatin, Capecitabine; 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; Drug: Oxaliplatin; Drug: Capecitabine
Active Comparator: Docetaxel, Oxaliplatin; 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: Docetaxel; Drug: Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Cancer Trials Ireland
• Investigators: Principal Investigator: Martin Eatock, Dr, Cancer Trials Ireland

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: October 15, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (Estimate): October 19, 2012

Study Record Updates

• Last Update Posted (Estimate): January 10, 2013
• Last Update Submitted That Met QC Criteria: January 8, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Capecitabine; Epirubicin; Oxaliplatin
• Other Study ID Numbers: ICORG 06-05