Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma (TRACC)

Multi-Modality Treatment of Resectable Oesophageal Adenocarcinoma Using Peri-operative Chemotherapy With Additional Pre-operative Combined Radiotherapy and Cetuximab

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.

Study Overview

• Status: Terminated
• Conditions: Resectable Esophageal Cancer
• Intervention / Treatment: Drug: cetuximab; Radiation: radiotherapy to oesophageal tumour

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584CX
    • UMC Utrecht

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:

• 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 cockcroft < 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pre-operative chemotherapy	Drug: cetuximab; 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; Other Names: erbitux; c225; Radiation: radiotherapy to oesophageal tumour; 45 Gy delivered in 25 fractions of 1.8 Gy 5d/wk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete remission	determination of tumor residual cell content in surgical specimen	1 month
Resectability rate defined as the number of patients abke to undergo resection after neo-adjuvant treatment		6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events during neo-adjuvant treatment as defined by NIH CTCAE v3.0	5 months
Complications in the post-operative period (defined as 4 weeks after surgery) that can be attributed to surgical procedures	4 weeks
Progression free survival and overall survival	5 years
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	5 years
The number of R0 resection determined by the pathologist	after surgery

Collaborators and Investigators

• Sponsor: P.O. Witteveen
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Principal Investigator: M. P. Lolkema, MD/PhD, UMC Utrecht

Publications and helpful links

General Publications

• Ubink I, van der Sluis P, Schipper M, Reerink O, Voest E, Borel-Rinkes I, Wijrdeman H, Vleggaar F, Agterof M, Overkleeft E, Siersema P, van Hillegersberg R, Lolkema MP. Adding preoperative radiotherapy plus cetuximab to perioperative chemotherapy for resectable esophageal adenocarcinoma: a single-center prospective phase II trial. Oncologist. 2014 Jan;19(1):32-3. doi: 10.1634/theoncologist.2013-0254. Epub 2013 Dec 12.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: January 22, 2009
• First Submitted That Met QC Criteria: January 22, 2009
• First Posted (Estimate): January 23, 2009

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: NL23124.041.08; 2008-002203-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No