Neoadjuvant Radiochemotherapy in Local Advanced Squamous Cell Carcinoma of the Esophagus With Weekly Cetuximab Plus Oxaliplatin Plus Continuous IV. 5-FU and Conventional Fractionated External Multi-Field Irradiation up to 45 Gray. A Phase I/II Study
18 Years
70 Years
Both
Esophageal Cancer
Trial Information
Neoadjuvant Radiochemotherapy in Local Advanced Squamous Cell Carcinoma of the Esophagus With Weekly Cetuximab Plus Oxaliplatin Plus Continuous IV. 5-FU and Conventional Fractionated External Multi-Field Irradiation up to 45 Gray. A Phase I/II Study
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of oxaliplatin and fluorouracil when administered
with cetuximab and radiotherapy in patients with stage II or III squamous cell
carcinoma of the esophagus. (Phase I)
- Determine the response rate in patients treated with this regimen. (Phase II)
Secondary
- Determine the toxicity of this regimen in these patients.
- Determine the postoperative complication rate and lethality in patients treated with
this regimen.
- Determine the R0 resection rate in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Determine the event-free survival of patients treated with this regimen.
- Determine the metabolic response rate in patients treated with this regimen.
OUTLINE: This is a phase I, dose-escalation study of oxaliplatin and fluorouracil followed
by an open-label, phase II study.
- Phase I: Patients receive cetuximab IV over 60-90 minutes on days -15, -8, 1, 8, 15,
22, and 29; oxaliplatin IV over 120 minutes on days 1, 8, 22, and 29; and fluorouracil
IV continuously on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients undergo
radiotherapy on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients then undergo radical
esophagectomy 29-42 days after the completion of chemoradiotherapy.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive oxaliplatin and fluorouracil as in phase I at the MTD
determined in phase I. Patients also receive cetuximab and undergo radiotherapy and
radical esophagectomy as in phase I.
After completion of study therapy, patients are followed every 3 months for 2 years and then
every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed squamous cell carcinoma of the esophagus, meeting the
following criteria:
- Locally advanced disease (T3-T4, N0-N+ [T2, N0 for cervical esophageal
carcinoma])
- Potentially resectable disease
- No distant metastases (M1b)
- No tumor infiltration of the tracheobronchial system
- Bartels preoperative risk analysis < 22
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
- Bilirubin ≤ 1.5 mg/dL
- ALT and AST ≤ 2 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN
- WBC ≥ 3,000/mm³
- Granulocyte count ≥ 2,000/mm³
- Platelet count ≥ 100,000/mm³
- No pre-existing polyneuropathy > grade 1
- No active uncontrolled infection
- PaO_2 ≥ 60 mm Hg on room air
- FEV_1 ≥ 60% of normal
- No New York Heart Association class II-IV cardiac insufficiency
- Ejection fraction ≥ 35%
- No angina pectoris (at rest or under stress) unexplained by interventional cardiology
- No myocardial infarction within the past 6 months
- No histologically confirmed liver cirrhosis
- No other malignancy within the past 5 years except carcinoma in situ of the cervix or
nonmelanomatous skin cancer
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy
- No prior radiotherapy to the thorax region
- No current esophageal stent
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of oxaliplatin and fluorouracil (Phase I)
Safety Issue:
Yes
Principal Investigator
Florian Lordick, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Technische Universität München
Authority:
Germany: BFARM
Study ID:
CDR0000516821
NCT ID:
NCT00425425
Start Date:
July 2006
Completion Date:
May 2015
Related Keywords:
- Esophageal Cancer
- squamous cell carcinoma of the esophagus
- stage IIA esophageal cancer
- stage IIB esophageal cancer
- stage IIIA esophageal cancer
- stage IIIB esophageal cancer
- stage IIIC esophageal cancer
- Carcinoma, Squamous Cell
- Esophageal Diseases
- Esophageal Neoplasms
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