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

Esophageal Cancer Clinical Trial

Official title:

Neoadjuvant Treatment for Operable Esophageal Cancer With 5-fluorouracil, Cisplatin, and Cetuximab and Concurrent Radiotherapy: Phase I/II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00544362
• Other study ID #: CDR0000564075
• Secondary ID: FFCD-0505EU-2075
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 13, 2007
• Last updated: May 27, 2016
• Start date: July 2007
• Est. completion date: March 2013

Study information

• Verified date: May 2016
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 2013
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• cisplatin

• fluorouracil

Procedure:
• conventional surgery

Locations

Country	Name	City	State
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Hopital Saint Andre	Bordeaux
France	C.H.U. de Brest	Brest
France	CHR Clermont Ferrand, Hotel Dieu	Clermont-Ferrand
France	Federation Francophone de Cancerologie Digestive	Dijon
France	Hopital Du Bocage	Dijon
France	Centre Hospital Universitaire Hop Huriez	Lille
France	Centre Oscar Lambret	Lille
France	CHU de la Timone	Marseille
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Centre Hospitalier Regional de Purpan	Toulouse
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete histologic response		After Surgery	No
Primary	Tolerance to neoadjuvant therapy		From Inclusion	Yes
Secondary	Progression-free and overall survival		From inclusion	No
Secondary	Mortality		From Inclusion	No