Fluorouracil, Cisplatin, Cetuximab, and Radiation Therapy in Treating Patients With Esophageal Cancer That Can Be Removed by Surgery
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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 |
Biological: cetuximab Drug: cisplatin Drug: fluorouracil Procedure: conventional surgery |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Neoadjuvant Treatment for Operable Esophageal Cancer With 5-fluorouracil, Cisplatin, and Cetuximab and Concurrent Radiotherapy: Phase I/II Study |
- Complete histologic response [ Time Frame: After Surgery ] [ Designated as safety issue: No ]
- Tolerance to neoadjuvant therapy [ Time Frame: From Inclusion ] [ Designated as safety issue: Yes ]
- Progression-free and overall survival [ Time Frame: From inclusion ] [ Designated as safety issue: No ]
- Mortality [ Time Frame: From Inclusion ] [ Designated as safety issue: No ]
| Enrollment: | 33 |
| Study Start Date: | July 2007 |
| Study Completion Date: | March 2013 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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
|
Biological: cetuximab Drug: cisplatin Drug: fluorouracil Procedure: conventional 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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00544362
| France | |
| Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz | |
| Besancon, France, 25030 | |
| Hopital Saint Andre | |
| Bordeaux, France, 33075 | |
| C.H.U. de Brest | |
| Brest, France, 29200 | |
| CHR Clermont Ferrand, Hotel Dieu | |
| Clermont-Ferrand, France, 63058 | |
| Hopital Du Bocage | |
| Dijon, France, 21034 | |
| Federation Francophone de Cancerologie Digestive | |
| Dijon, France, 21079 | |
| Centre Oscar Lambret | |
| Lille, France, 59020 | |
| Centre Hospital Universitaire Hop Huriez | |
| Lille, France, 59037 | |
| CHU de la Timone | |
| Marseille, France, 13385 | |
| Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle | |
| Montpellier, France, 34298 | |
| Centre Hospitalier Lyon Sud | |
| Pierre Benite, France, 69495 | |
| Centre Hospitalier Regional de Purpan | |
| Toulouse, France, 31059 | |
| Centre Alexis Vautrin | |
| Vandoeuvre-les-Nancy, France, 54511 | |
| Study Chair: | Martina Schneider | Federation Francophone de Cancerologie Digestive |
More Information
| Responsible Party: | Federation Francophone de Cancerologie Digestive |
| ClinicalTrials.gov Identifier: | NCT00544362 History of Changes |
| Other Study ID Numbers: | CDR0000564075 FFCD-0505 EU-20756 EUDRACT-2006-004770-27 MERCK-FFCD-0505 |
| Study First Received: | October 13, 2007 |
| Last Updated: | May 27, 2016 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by Federation Francophone de Cancerologie Digestive:
|
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 |
Additional relevant MeSH terms:
|
Esophageal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Head and Neck Neoplasms Digestive System Diseases Esophageal Diseases Gastrointestinal Diseases Cisplatin |
Cetuximab Fluorouracil Antineoplastic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on September 27, 2016