Cetuximab, Oxaliplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Stage II or Stage III Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00425425
Recruitment Status : Unknown
Verified April 2014 by Technische Universität München.
Recruitment status was:  Active, not recruiting
First Posted : January 23, 2007
Last Update Posted : May 1, 2014
Information provided by:
Technische Universität München

Brief Summary:

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab, chemotherapy, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin and fluorouracil when given together with cetuximab and radiation therapy and to see how well they work in treating patients with stage II or stage III esophageal cancer.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Biological: cetuximab Drug: fluorouracil Drug: oxaliplatin Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy Phase 1 Phase 2

Detailed Description:



  • 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)


  • 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2006
Actual Primary Completion Date : May 2010
Estimated Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Maximum tolerated dose of oxaliplatin and fluorouracil (Phase I)
  2. Response rate (histological remission) (Phase II)

Secondary Outcome Measures :
  1. Toxicity as measured by NCI-CTC criteria
  2. Postoperative complication rate and lethality
  3. R0 resection rate
  4. Overall survival
  5. Event-free survival
  6. Metabolic response rate

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • No prior chemotherapy
  • No prior radiotherapy to the thorax region
  • No current esophageal stent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00425425

Charite University Hospital - Campus Virchow Klinikum
Berlin, Germany, D-13353
Universitaetsklinikum Giessen und Marburg GmbH - Marburg
Marburg, Germany, D-35033
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Sponsors and Collaborators
Technische Universität München
Study Chair: Florian Lordick, MD Technische Universität München Identifier: NCT00425425     History of Changes
Other Study ID Numbers: CDR0000516821
First Posted: January 23, 2007    Key Record Dates
Last Update Posted: May 1, 2014
Last Verified: April 2014

Keywords provided by Technische Universität München:
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

Additional relevant MeSH terms:
Esophageal Neoplasms
Carcinoma, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs