Fluorouracil, Cisplatin, Cetuximab, and Radiation Therapy in Treating Patients With Esophageal Cancer That Can Be Removed by Surgery - Full Text View

Sponsored by:	Federation Francophone de Cancerologie Digestive
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00544362

Purpose

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving fluorouracil and cisplatin together with cetuximab and radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of fluorouracil and cisplatin when given together with cetuximab and radiation therapy in treating patients with esophageal cancer that can be removed by surgery.

Condition	Intervention	Phase
Esophageal Cancer	Drug: cetuximab Drug: cisplatin Drug: fluorouracil Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase I Phase II

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Cisplatin Fluorouracil Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	Neoadjuvant Treatment for Operable Esophageal Cancer With 5-Fluorouracil, Cisplatin, and Cetuximab and Concurrent Radiotherapy: Phase I/II Study

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete histologic response [ Designated as safety issue: No ]
Tolerance to neoadjuvant therapy [ Designated as safety issue: Yes ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression-free and overall survival [ Designated as safety issue: No ]
Complete resection with negative margins (R0) [ Designated as safety issue: No ]
Mortality [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	July 2007

Detailed Description:

OBJECTIVES:

Primary

To determine the maximum tolerated dose of fluorouracil and cisplatin when administered with cetuximab concurrently with esophageal radiotherapy. (Phase I)
To determine the complete histological response rate (after surgical resection). (Phase II)

Secondary

To determine progression-free survival and overall survival. (Phase II)
To determine the rate of resection with negative margins (R0). (Phase II)
To determine the overall tolerance to neoadjuvant therapy. (Phase II)
To determine the postoperative morbidity and mortality. (Phase II)

OUTLINE: This is a multicenter study. This is a dose-escalation study of cisplatin and fluorouracil.

Patients receive cetuximab IV over 2 hours on day -7, then IV over 1 hour on days 1, 8, 15, 22, and 29. Patients also receive cisplatin IV over 1 hour on day 1 or 2 and fluorouracil IV continuously on days 1-4, 8-11, 15-18, 22-25, and 29-32. Patients undergo radiotherapy 5 days a week for 5 weeks, beginning on day 1 of chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo surgery within 6-8 weeks after completion of chemoradiotherapy.

After completion of study therapy, patients are followed at 1 month, every 4 months for 2 years, and then every 6 months for 2 years.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

Histologically confirmed epidermoid or glandular carcinoma of the thoracic esophagus
- Invasive disease
- Only Siewert type I gastroesophageal carcinoma allowed
Resectable disease
- T1N+, T2N0, T2N+, T3N0, or T3N+ (stage II or III)
- No visceral metastases or mediastinal extensions compromising resectability

Exclusion criteria:

Inoperable disease
Invasion of the tracheo-bronchial tree
Recurring esophageal paralysis
Esopho-tracheal fistula
Cervical esophageal carcinoma (< 19 cm above the dental arches)
Multifocal esophageal carcinoma
Superficial esophageal carcinoma (T1N0)
Esophageal carcinoma in the lymph nodes that cannot be included in the radiotherapy field or cannot be completely surgically resected
Proven metastatic disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

WHO performance status 0-1
Weight loss < 15%
Absolute neutrophil count ≥ 1,500/mm3
Platelet count ≥ 100,000/mm3
Creatinine ≤ 1.25 times upper limit of normal
PTT ≥ 80%
Albumin ≥ 35 g/L
FEV1 > 1 L
Not pregnant or nursing
Fertile patients of must use effective contraception

Exclusion criteria:

Known liver cirrhosis
Renal insufficiency
Respiratory insufficiency (i.e., severe dyspnea at rest or oxygen dependence)
Progressive coronary insufficiency
Myocardial infarction in the past 6 months
Legally incapacitated
Impossible to receive study therapy due to geographical, social, or psychological reasons
Noncompliant within constraints of the study
Hematologic malignancy or other cancer except carcinoma in situ of the uterine cervix, treated nonmelanoma skin cancer, or intramucous disease treated within the past 3 years

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

Prior anticancer chemotherapy or radiotherapy
Treatment with endoprosthesis
Surgery (esophagectomy) planned without thoracotomy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00544362

Locations

France
C.H.U. de Brest	Recruiting
Brest, France, 29200
Contact: Jean-Philippe Metges, MD 33-2-9822-3333
Centre Alexis Vautrin	Recruiting
Vandoeuvre-les-Nancy, France, 54511
Contact: Thierry Conroy, MD 33-3-8359-8460
Centre Hospital Universitaire Hop Huriez	Recruiting
Lille, France, 59037
Contact: Christophe Mariette, MD, PhD 33-32-44-4407 c-mariette@chru-lille.fr
Centre Hospitalier Lyon Sud	Recruiting
Pierre Benite, France, 69495
Contact: Francoise Mornex, MD, PhD 33-478-864-253 francoise.mornex@chu-lyon.fr
Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Recruiting
Besancon, France, 25030
Contact: Thanh Van N'Guyen 33-81-668-240
Centre Hospitalier Regional de Purpan	Recruiting
Toulouse, France, 31059
Contact: Nicolas Carrere, MD, PhD 33-56-177-7610 carrere.n@chu-toulouse.fr
Hopital Saint Andre	Recruiting
Bordeaux, France, 33075
Contact: Veronique Vendrely 33-5-5679-5808
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Recruiting
Montpellier, France, 34298
Contact: Marc Ychou, MD, PhD 33-4-6761-3066 mychou@valdorel.fnclcc.fr
CHR Clermont Ferrand, Hotel Dieu	Recruiting
Clermont-Ferrand, France, 63058
Contact: Denis Pezet, MD 33-73-750-494 dpezet@chu-clermontferrand.fr
CHU de la Timone	Recruiting
Marseille, France, 13385
Contact: Jean-Francois Seitz, MD 33-4-9138-6023
Federation Francophone de Cancerologie Digestive	Recruiting
Dijon, France, 21079
Contact: Martina Schneider 33-3-8039-3483
Hopital Du Bocage	Recruiting
Dijon, France, 21034
Contact: Jean-Louis Jouve 33-3-8029-3750
Centre Oscar Lambret	Recruiting
Lille, France, 59020
Contact: Antoine Adenis, MD, PhD 33-320-29-59-42 a-adenis@o-lambret.fr

Sponsors and Collaborators

Federation Francophone de Cancerologie Digestive

Investigators

Study Chair:

Martina Schneider

Federation Francophone de Cancerologie Digestive

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000564075, FFCD-0505, EU-20756, EUDRACT-2006-004770-27, MERCK-FFCD-0505
Study First Received:	October 13, 2007
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00544362
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage III esophageal cancer
stage IV esophageal cancer
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus

Study placed in the following topic categories:

Digestive System Neoplasms
Esophageal disorder
Gastrointestinal Diseases
Esophageal Neoplasms
Squamous cell carcinoma
Cetuximab
Carcinoma
Epidermoid carcinoma
Digestive System Diseases

Cisplatin
Fluorouracil
Head and Neck Neoplasms
Carcinoma, squamous cell
Gastrointestinal Neoplasms
Esophageal Diseases
Carcinoma, Squamous Cell
Adenocarcinoma
Esophageal neoplasm

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site
Immunologic Factors
Molecular Mechanisms of Pharmacological Action

Radiation-Sensitizing Agents
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009