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

Esophageal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00425425
• Other study ID #: CDR0000516821
• Secondary ID: KRDI-TUM-OE7-432
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: January 19, 2007
• Last updated: April 30, 2014
• Start date: July 2006
• Est. completion date: May 2015

Study information

• Verified date: April 2014
• Source: Technische Universität München
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: BFARM
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 43
• Est. completion date: May 2015
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• fluorouracil

• oxaliplatin

Procedure:
• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Germany	Charite University Hospital - Campus Virchow Klinikum	Berlin
Germany	Universitaetsklinikum Giessen und Marburg GmbH - Marburg	Marburg
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität München

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of oxaliplatin and fluorouracil (Phase I)			Yes
Primary	Response rate (histological remission) (Phase II)			No
Secondary	Toxicity as measured by NCI-CTC criteria			Yes
Secondary	Postoperative complication rate and lethality			No
Secondary	R0 resection rate			No
Secondary	Overall survival			No
Secondary	Event-free survival			No
Secondary	Metabolic response rate			No