Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma - Full Text View

Sponsors and Collaborators:	UMC Utrecht Merck KGaA
Information provided by:	UMC Utrecht
ClinicalTrials.gov Identifier:	NCT00827671

Purpose

The purpose of this study is to determine whether the addition of the combination between cetuximab and radiotherapy to the standard chemotherapy for resectable oesophageal cancer is safe and adds efficacy.

Condition	Intervention	Phase
Resectable Esophageal Cancer	Drug: cetuximab Radiation: radiotherapy to oesophageal tumour	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Multi-Modality Treatment of Resectable Oesophageal Adenocarcinoma Using Peri-Operative Chemotherapy With Additional Pre-Operative Combined Radiotherapy and Cetuximab

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Radiation Therapy

Drug Information available for: Cetuximab

U.S. FDA Resources

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:

pathological complete remission [ Time Frame: after surgery ] [ Designated as safety issue: No ]
Resectability rate defined as the number of patients abke to undergo resection after neo-adjuvant treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Adverse events during neo-adjuvant treatment as defined by NIH CTCAE v3.0 [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
Complications in the post-operative period (defined as 4 weeks after surgery) that can be attributed to surgical procedures [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Progression free survival and overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Define local (locoregional lymphnode metastasis as defined by TNM classification/ malignant peritonitis/ solid masses within the anatomic region of the esophagus) vs distant metastases as first manifestation of recurrence [ Time Frame: 5 years ] [ Designated as safety issue: No ]
The number of R0 resection determined by the pathologist [ Time Frame: after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	March 2009
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Intervention Details:

cetuximab initial dose 400 mg/m2 iv 1 week before start radiotherapy and subsequent weekly doses of 250 mg/m2 iv for the duration of the radiation treatment

45 Gy delivered in 25 fractions of 1.8 Gy 5d/wk

Detailed Description:

This study aims at developing a novel strategy to optimize the treatment of oesophageal adenocarcinoma and gastro-oesophageal junctional tumors with curative intent. Surgery in combination with peri-operative chemotherapy, using the combination epirubicin, cisplatin and 5-FU, as defined by the recent MAGIC trial, results in 13% increase in 5-yr survival. To improve the outcome of patients with this disease we hypothesize that the addition of pre-operative combined cetuximab-radiotherapy (cetux-RT) treatment could improve the outcome of this patient category through better local control.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically proven resectable adenocarcinoma of the lower oesophagus and gastric-oesophageal junction
Tumour stage: T2-3 N0-1 M0, as assessed by endoscopic ultrasound and CT-scan of thorax and abdomen and ultrasound neck region. For the patients treated in this study the gastro-oesophageal junctional tumors will be staged as oesophageal tumors with respect to their lymphnode metastases.
Age >18y and written informed consent after at least 4 days of deliberation time from the moment the patient information has been given and has been explained.
Weight loss < 10% in 0.5 yr
WHO performance status 0-1
No prior radiotherapy or chemotherapy for the adenocarcinoma of the oesophagus

Exclusion Criteria:

Previous malignancy other than basal cell carcinoma of the skin or local resection for cervical carcinoma in situ.
Inadequate organ function as defined by:
Inadequate haematology (Hb < 5,5 mmol/L (red blood cell transfusions are allowed to increase the Hb at the discretion of the investigator) - neutrophils < 1,5 109/L -platelets <100*109/L),
Liver enzyme elevation (bili > 1,5*ULN - ASAT > 2,5*ULN - ALAT > 2,5*ULN) or
Impaired renal function (creatinine clearance by cockroft < 60 cc/min)
Proteinuria >1,0gr/24hr
Tumour stage: M1a and/or tumour length > 8 cm and/or > 5 cm radially
Major surgery within 4 weeks prior to the start of study treatment
Bleeding disorder
Known allergy to one of the study drugs used
Use of any substance known to interfere with the chemotherapy clearance
Previous radiotherapy to the chest
Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments
Uncontrolled angina pectoris; cardiac failure or clinically significant arrhythmias
Continuous use of immunosuppressive agents
Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine
Prior exposure to anti-EGFR targeting agents.
Hearing loss > 25 dB under normal
Neurotoxicity > CTC grade 1
Pregnancy or breast feeding
Patients (M/F) with reproductive potential not implementing adequate contraceptive measures

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827671

Contacts

Contact: M. P. Lolkema, MD/PhD	0031307556265	m.p.j.k.lolkema@umcutrecht.nl
Contact: E. E. Voest, MD/PhD	0031307556265	e.e.voest@umcutrecht.nl

Locations

Netherlands
UMC Utrecht	Recruiting
Utrecht, Netherlands, 3584CX
Principal Investigator: M. P. Lolkema, MD/PhD
Sub-Investigator: E. E. Voest, MD/PhD
Sub-Investigator: R van Hilligersberg, MD/PhD
Sub-Investigator: O Reerink, MD/PhD
Sub-Investigator: M E Schipper, MD/PhD
Sub-Investigator: P D Siersema, MD/PhD

Sponsors and Collaborators

UMC Utrecht

Merck KGaA

Investigators

Principal Investigator:

M. P. Lolkema, MD/PhD

UMC Utrecht

More Information

No publications provided

Responsible Party:	UMC Utrecht ( Dr. M.P.J.K. Lolkema )
Study ID Numbers:	NL23124.041.08, EudraCT number: 2008-002203-13
Study First Received:	January 22, 2009
Last Updated:	March 12, 2009
ClinicalTrials.gov Identifier:	NCT00827671 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study placed in the following topic categories:

Digestive System Neoplasms
Gastrointestinal Diseases
Esophageal Neoplasms
Cetuximab
Esophageal Cancer
Carcinoma
Digestive System Diseases

Esophageal Disorder
Head and Neck Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Digestive System Neoplasms
Antineoplastic Agents
Gastrointestinal Diseases
Esophageal Neoplasms
Cetuximab
Pharmacologic Actions
Carcinoma
Neoplasms

Digestive System Diseases
Neoplasms by Site
Therapeutic Uses
Head and Neck Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009