Clinical trial NCT00544362: Fluorouracil, Cisplatin, Cetuximab, and Radiation Therapy in Treating Patients With Esophageal Cancer That Can Be Removed by Surgery
Official title: Neoadjuvant Treatment for Operable Esophageal Cancer With 5-fluorouracil, Cisplatin, and Cetuximab and Concurrent Radiotherapy: Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
stage IV esophageal cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2007-10-16
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Complete histologic response
timeFrame: After Surgery
measure: Tolerance to neoadjuvant therapy
timeFrame: From Inclusion
Secondary outcomes:
measure: Progression-free and overall survival
timeFrame: From inclusion
measure: Mortality
timeFrame: From Inclusion
Other outcomes:
Locations:
city: Besancon
country: France
facility: Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Brest
country: France
facility: C.H.U. de Brest
city: Clermont-Ferrand
country: France
facility: CHR Clermont Ferrand, Hotel Dieu
city: Dijon
country: France
facility: Hopital Du Bocage
city: Dijon
country: France
facility: Federation Francophone de Cancerologie Digestive
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Centre Hospital Universitaire Hop Huriez
city: Marseille
country: France
facility: CHU de la Timone
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Toulouse
country: France
facility: Centre Hospitalier Regional de Purpan
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
Study officials:
affiliation: Federation Francophone de Cancerologie Digestive
name: Martina Schneider
role: STUDY_CHAIR
References: