Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma (TRACC)
Primary Purpose
Resectable Esophageal Cancer
Status
Terminated
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
cetuximab
radiotherapy to oesophageal tumour
Sponsored by

About this trial
This is an interventional treatment trial for Resectable Esophageal Cancer
Eligibility 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 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
Sites / Locations
- UMC Utrecht
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Pre-operative chemotherapy
Arm Description
Outcomes
Primary Outcome Measures
pathological complete remission
determination of tumor residual cell content in surgical specimen
Resectability rate defined as the number of patients abke to undergo resection after neo-adjuvant treatment
Secondary Outcome Measures
Adverse events during neo-adjuvant treatment as defined by NIH CTCAE v3.0
Complications in the post-operative period (defined as 4 weeks after surgery) that can be attributed to surgical procedures
Progression free survival and overall survival
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
The number of R0 resection determined by the pathologist
Full Information
NCT ID
NCT00827671
First Posted
January 22, 2009
Last Updated
March 7, 2018
Sponsor
P.O. Witteveen
Collaborators
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00827671
Brief Title
Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma
Acronym
TRACC
Official Title
Multi-Modality Treatment of Resectable Oesophageal Adenocarcinoma Using Peri-operative Chemotherapy With Additional Pre-operative Combined Radiotherapy and Cetuximab
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Terminated
Why Stopped
Experimental treatment not feasible due to high rate of drop out
Study Start Date
March 2009 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
P.O. Witteveen
Collaborators
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resectable Esophageal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pre-operative chemotherapy
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
cetuximab
Other Intervention Name(s)
erbitux, c225
Intervention Description
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
Intervention Type
Radiation
Intervention Name(s)
radiotherapy to oesophageal tumour
Intervention Description
45 Gy delivered in 25 fractions of 1.8 Gy 5d/wk
Primary Outcome Measure Information:
Title
pathological complete remission
Description
determination of tumor residual cell content in surgical specimen
Time Frame
1 month
Title
Resectability rate defined as the number of patients abke to undergo resection after neo-adjuvant treatment
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Adverse events during neo-adjuvant treatment as defined by NIH CTCAE v3.0
Time Frame
5 months
Title
Complications in the post-operative period (defined as 4 weeks after surgery) that can be attributed to surgical procedures
Time Frame
4 weeks
Title
Progression free survival and overall survival
Time Frame
5 years
Title
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
Title
The number of R0 resection determined by the pathologist
Time Frame
after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M. P. Lolkema, MD/PhD
Organizational Affiliation
UMC Utrecht
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMC Utrecht
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
24335595
Citation
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.
Results Reference
derived
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Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma
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