Cisplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients With Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

A Randomised Phase II/III Multi-Centre Clinical Trial of Definitive Chemotherapy, With or Without Cetuximab, in Carcinoma of the Oesophagus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00509561
• Other study ID #: CDR0000558804
• Secondary ID: WCTU-SCOPE-1EU-2
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: July 30, 2007
• Last updated: December 17, 2012
• Start date: February 2008

Study information

• Verified date: December 2012
• Source: Wales Cancer Trials Unit
• Contact: n/a
• Is FDA regulated: No
• Health authority: Medicines and Healthcare Products Regulatory Agency, United Kingdom:
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and capecitabine, work in different ways to kill tumor cells or stop them from growing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving cisplatin together with capecitabine and radiation therapy is more effective with or without cetuximab in treating esophageal cancer.

PURPOSE: This randomized phase II/III trial is studying the side effects and how well giving cisplatin together with capecitabine, radiation therapy, and cetuximab works compared with giving cisplatin, capecitabine, and radiation therapy without cetuximab in treating patients with esophageal cancer.

Description:

OBJECTIVES:

Primary

• To determine whether the addition of cetuximab to definitive chemoradiotherapy comprising cisplatin, capecitabine, and radiotherapy shows evidence of enhanced overall survival in patients with carcinoma of the esophagus.

• To determine the safety of this regimen in these patients.

• To determine the feasibility of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-84. Beginning in week 7 patients also undergo radiotherapy 5 days a week for 5 weeks (weeks 7-11). Treatment continues in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive cisplatin and capecitabine and undergo radiotherapy as in arm I. Patients also receive cetuximab IV over 1-2 hours on day 1 in weeks 1-12. Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life and health economics are assessed at baseline, during treatment, and at pre-specified time points during follow-up.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then annually for a minimum of 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 259
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the esophagus

• Adenocarcinoma

• Squamous cell

• Undifferentiated carcinoma

• Siewert type I tumor of the gastroesophageal junction

• Localized, nonmetastatic disease (T1-4, N0-1) confirmed by endoscopic ultrasound (EUS) and spiral CT scan

• Total disease length (primary and lymph nodes) < 10 cm by EUS

• Not suitable for surgery (either for medical reasons or patient's choice)

• No metastatic disease (i.e., M1a or M1b according to UICC TNM version 6)

• No significant (> 2 cm) extension of tumor into the stomach

PATIENT CHARACTERISTICS:

• WHO performance status 0-1

• Absolute neutrophil count = 1,500/mm³

• White blood cell count = 2,000/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 10 g/dL (should be corrected to > 10 g/dL before treatment)

• Serum bilirubin = 1.5 times upper limit of normal (ULN)

• ALT/AST = 2.5 times ULN

• Alkaline phosphatase = 3 times ULN

• Glomerular filtration rate > 40 mL/min OR > 60 mL/min estimated by Cockcroft-Gault formula

• Adequate cardiac ejection fraction = 40% by MUGA or ECHO

• FEV_1 = 1 L by spirometry

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception

• No malignancy within the past 5 years

• No unstable angina, uncontrolled hypertension, cardiac failure, or other clinically significant cardiac disease

• No major trauma within the past 4 weeks

• No known dihydropyrimidine dehydrogenase deficiency

• No hearing impairment or sensory-motor neuropathy > grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 4 weeks since prior sorivudine and analogues

• At least 4 weeks since prior major surgery

• At least 4 weeks since prior monoclonal antibody

• At least 3 months since prior radiotherapy

• No prior treatment for invasive esophageal carcinoma or gastroesophageal junction carcinoma (not including photodynamic therapy or laser therapy for high-grade dysplasia/carcinoma in situ)

• No other prior treatment for this malignancy that would compromise the ability to deliver definitive mediastinal chemoradiotherapy or compromise survival

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• capecitabine

• cisplatin

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Belfast	Northern Ireland
United Kingdom	Good Hope Hospital	Birmingham	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Cumberland Infirmary	Carlisle	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Gloucestershire Royal Hospital	Cheltenham	England
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Princess Alexandra Hospital	Essex	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	Raigmore Hospital	Inverness	Scotland
United Kingdom	Cookridge Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Lincoln County Hospital	Lincoln	England
United Kingdom	Aintree University Hospital	Liverpool	England
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Helen Rollason Cancer Care Centre at North Middlesex Hospital	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Peterborough Hospitals Trust	Peterborough	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Portsmouth Oncology Centre at Saint Mary's Hospital	Portsmouth Hants	England
United Kingdom	Alexandra Healthcare NHS	Redditch	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Scarborough General Hospital	Scarborough	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Wexham Park Hospital	Slough, Berkshire	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Southport and Formby District General Hospital	Southport	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Singleton Hospital	Swansea	Wales
United Kingdom	Musgrove Park Hospital	Taunton	England
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	Worcester Royal Hospital	Worcester	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales

Sponsors (2)

Lead Sponsor	Collaborator
Wales Cancer Trials Unit	Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-failure rate at 24 weeks			No
Primary	Overall survival			No
Secondary	Feasibility			No
Secondary	Toxicity			Yes
Secondary	Quality of life			No
Secondary	Quality of assurance			No
Secondary	Health economics			No