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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Technische Universität München
ClinicalTrials.gov Identifier:
NCT00425425
First received: January 19, 2007
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Esophageal Cancer
Biological: cetuximab
Drug: fluorouracil
Drug: oxaliplatin
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by Technische Universität München:

Primary Outcome Measures:
  • Maximum tolerated dose of oxaliplatin and fluorouracil (Phase I) [ Designated as safety issue: Yes ]
  • Response rate (histological remission) (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as measured by NCI-CTC criteria [ Designated as safety issue: Yes ]
  • Postoperative complication rate and lethality [ Designated as safety issue: No ]
  • R0 resection rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]
  • Metabolic response rate [ Designated as safety issue: No ]

Estimated Enrollment: 43
Study Start Date: July 2006
Estimated Study Completion Date: May 2015
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00425425

Locations
Germany
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
Investigators
Study Chair: Florian Lordick, MD Technische Universität München
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00425425     History of Changes
Other Study ID Numbers: CDR0000516821, KRDI-TUM-OE7-432-LOR-0033-I, EU-20658, EUDRACT-2006-001097-24
Study First Received: January 19, 2007
Last Updated: April 30, 2014
Health Authority: Germany: BFARM

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:
Carcinoma, Squamous Cell
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Fluorouracil
Oxaliplatin
Cetuximab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014