Cetuximab in Combination With Radiation Therapy and Chemotherapy Prior to Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma. A Multicenter Phase IB-II Trial
18 Years
70 Years
Both
Esophageal Cancer
Trial Information
Cetuximab in Combination With Radiation Therapy and Chemotherapy Prior to Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma. A Multicenter Phase IB-II Trial
OBJECTIVES:
Primary
- Determine the safety of neoadjuvant radiotherapy in combination with cetuximab,
docetaxel, and cisplatin in patients with resectable locally advanced esophageal
cancer.
Secondary
- Determine the feasibility and efficacy of this regimen in these patients.
- Determine the duration of response and patterns of failure in patients treated with
this regimen.
OUTLINE: This is a multicenter study.
- Chemoimmunotherapy: Patients receive cetuximab IV over 1-2 hours once weekly in weeks
1-3 and docetaxel IV over 1 hour and cisplatin IV over 1 hour once in week 1. Treatment
repeats every 3 weeks for 2 courses.
- Chemoimmunotherapy and radiotherapy: Patients are sequentially assigned to 1 of 2
treatment levels.
- Treatment level 1: Patients receive cetuximab IV over 1 hour once weekly,
cisplatin IV over 1 hour once weekly, and undergo radiotherapy once daily, 5 days
a week, in weeks 7-11.
- Treatment level 2: Patients receive cetuximab, cisplatin, and radiotherapy as in
treatment level 1. Patients also receive docetaxel IV over 1-2 hours once weekly
in weeks 7-11.
Cohorts of 7-20 patients are treated at treatment level 1 or 2 sequentially, as long as no
more than 2 of 7 patients experience dose-limiting toxicity (DLT), until the safe treatment
level for future study is determined. The safe treatment level is defined as the level at
which no more than 2 of 7 and no more than 6 of 20 patients experience DLT. At least 20
patients are treated at the safe treatment level.
- Surgery: Between 4-8 weeks after completion of neoadjuvant chemoimmunotherapy and
radiotherapy, patients undergo surgery.
After completion of study treatment, patients are followed every 3 months for 1 year, every
6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic
esophagus
- Carcinoma of the gastroesophageal junction (i.e., Siewert staging system type I
disease) allowed
- Locally advanced disease
- Obstructive tumors are considered locally advanced disease
- Meets 1 of the following staging criteria:
- T3, N0 disease
- T1-3, N1 disease
- T4, N0-1 disease
- Resectable disease
- No T4 (unequivocal organ involvement) disease that cannot be resected with
curative intent
- No airway infiltration in case of tumors of the upper third of the thoracic esophagus
- No cervical esophageal carcinoma
- No distant metastasis, including stage M1a (celiac node involvement) by fine-needle
aspiration or biopsy
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Creatinine clearance > 60 mL/min
- Bilirubin normal
- Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
- AST ≤ 1.5 times ULN
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 12 months after
completion of study treatment
- No other malignancy within the past 5 years except nonmelanomatous skin cancer or
adequately treated in situ cervical cancer
- No severe or uncontrolled cardiovascular disease including, but not limited to, any
of the following:
- New York Heart Association class III or IV congestive heart failure
- Unstable angina pectoris
- Myocardial infarction within the past 3 months
- Significant arrhythmias
- No psychiatric disorder that would preclude study compliance
- No active uncontrolled infection
- No serious underlying medical condition that, in the opinion of the investigator,
would interfere with study participation (e.g., uncontrolled diabetes mellitus or
active autoimmune disease)
- No peripheral neuropathy > grade 1
- No contraindications to corticosteroids
- No known hypersensitivity to any component of the study drugs
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy
- No prior radiotherapy to the chest
- No participation in another clinical trial within the past 30 days
- No other concurrent experimental drugs or anticancer therapy
- No concurrent drugs contraindicated for use with the study drugs
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin
Outcome Description:
Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin
Outcome Time Frame:
Until treatment ends
Safety Issue:
Yes
Principal Investigator
Thomas Ruhstaller, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Kantonsspital St. Gallen
Authority:
Switzerland: Swissmedic
Study ID:
SAKK 75/06
NCT ID:
NCT00445861
Start Date:
January 2007
Completion Date:
November 2008
Related Keywords:
- Esophageal Cancer
- adenocarcinoma of the esophagus
- squamous cell carcinoma of the esophagus
- stage II esophageal cancer
- stage III esophageal cancer
- Esophageal Diseases
- Esophageal Neoplasms
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