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

NCT ID: NCT00544362

Last Updated: 2016-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2013-03-31

Brief 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.

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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant chemoradiotherapy

Weekly cetuximab (400 mg/m2 one week before start of radiotherapy RT and 250 mg/m2 during radiotherapyRT), and 5 FU (500 mg/m2 per day D1-D4) combined with cisplatin CDDP (40 mg/m2 D1) on week 1 and 5

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

Interventions

cetuximab

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

Eligibility Criteria

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

• 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

• 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:

• 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:

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martina Schneider

Role: STUDY_CHAIR

Federation Francophone de Cancerologie Digestive

Locations

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, , France

Hopital Saint Andre

Bordeaux, , France

C.H.U. de Brest

Brest, , France

CHR Clermont Ferrand, Hotel Dieu

Clermont-Ferrand, , France

Hopital Du Bocage

Dijon, , France

Federation Francophone de Cancerologie Digestive

Dijon, , France

Centre Oscar Lambret

Lille, , France

Centre Hospital Universitaire Hop Huriez

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-Bénite, , France

Centre Hospitalier Regional de Purpan

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

FFCD-0505

Identifier Type: -

Identifier Source: secondary_id

EU-20756

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2006-004770-27

Identifier Type: -

Identifier Source: secondary_id

MERCK-FFCD-0505

Identifier Type: -

Identifier Source: secondary_id

CDR0000564075

Identifier Type: -

Identifier Source: org_study_id