Clinical trial NCT00509561: Cisplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients With Esophageal Cancer
Official title: A Randomised Phase II/III Multi-Centre Clinical Trial of Definitive Chemotherapy, With or Without Cetuximab, in Carcinoma of the Oesophagus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage IA esophageal cancer
stage IB esophageal cancer
stage IIA esophageal cancer
stage IIB esophageal cancer
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
Lead sponsor: Wales Cancer Trials Unit
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2007-07-31
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-failure rate at 24 weeks
measure: Overall survival
Secondary outcomes:
measure: Feasibility
measure: Toxicity
measure: Quality of life
measure: Quality of assurance
measure: Health economics
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Birmingham
country: United Kingdom
facility: Good Hope Hospital
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Carlisle
country: United Kingdom
facility: Cumberland Infirmary
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Essex
country: United Kingdom
facility: Princess Alexandra Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Helen Rollason Cancer Care Centre at North Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Redditch
country: United Kingdom
facility: Alexandra Healthcare NHS
state: England
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Southport
country: United Kingdom
facility: Southport and Formby District General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Worcester
country: United Kingdom
facility: Worcester Royal Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust Incorporating Belvoir Park Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
state: Wales
Study officials:
affiliation: Velindre NHS Trust
name: Tom Crosby, MD
role: STUDY_CHAIR
References: