Clinical trial NCT00047112: Surgery With or Without Radiation Therapy and Chemotherapy in Treating Patients With Esophageal Cancer
Official title: Randomized Study of Pre-Operative Radio-Chemotherapy Versus Surgery Alone in Thoracic Esophageal Cancer Deemed to be Resectable
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage I esophageal cancer
stage II esophageal cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
Collaborators: name: GERCOR - Multidisciplinary Oncology Cooperative Group
name: European Organisation for Research and Treatment of Cancer - EORTC
name: UNICANCER
name: Societe Francaise de Radiotherapie Oncologique
First posted: 2003-01-27
Enrollment: 195
Sex: ALL
Maximum age (years): 74
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so it can be removed during surgery. It is not yet known if surgery is more effective with or without radiation therapy and chemotherapy in treating esophageal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without radiation therapy and chemotherapy in treating patients who have esophageal cancer.

Detailed description: OBJECTIVES:

* Compare the overall survival of patients with resectable thoracic esophageal cancer treated with neoadjuvant radio-chemotherapy and surgery versus surgery alone.
* Compare the disease-free survival of patients treated with these regimens.
* Compare the surgical mortality and morbidity of patients treated with these regimens.
* Compare the resectability of patients treated with these regimens.
* Determine the validation of new prognostic factors for survival of these patients and/or the efficacy of this neoadjuvant treatment.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to histology (epidermoid carcinoma vs adenocarcinoma vs undifferentiated carcinoma), stage (I vs IIA vs IIB), tumor location (above the carina vs below the carina), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo radiotherapy daily 5 days a week for 5 weeks. Patients receive fluorouracil IV continuously on days 1-4 and 29-32 and cisplatin IV on days 1 or 2 and 29 or 30 (or a lower dose on days 1-5 and 29-33). Within 4-8 weeks after completion of radio-chemotherapy, patients undergo surgical resection.
* Arm II: Patients undergo surgical resection. Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 380 patients (190 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of stage I or II thoracic esophageal cancer

  * Tumor no greater than 3 cm with no invasion of mediastinal structures with or without extension to the lymph nodes (T1-2, N0-1, M0) OR
  * Tumor greater than 3 cm with no invasion of mediastinal structures and no adenopathy greater than 1 cm (T3, N0, M0)
  * Epidermoid carcinoma or adenocarcinoma
* Previously untreated
* Deemed resectable with curative intent
* No carcinoma in situ
* No small cell anaplastic carcinoma (i.e., chromogranin negative)
* No small cell neuroendocrine carcinoma (i.e., chromogranin positive)
* No multifocal esophageal carcinoma (i.e., 2 or more distinct lesions 5 or more cm apart)
* No involvement of the pharyngoesophageal junction and the first 4 cm of the esophagus (i.e., where the proximal edge of the tumor is less than 19 cm from the dental arch)
* No evidence of extension to the tracheobronchial tree at endoscopy, ultrasound, or CT scan (simple compression allowed)
* No signs of mediastinal involvement on CT scan
* No palpable subclavicular lymph nodes or involvement after cytology needle aspiration
* No lymph nodes from the origin of the celiac greater than 1 cm on CT scan

  * Perigastric lymph nodes far from the celiac trunk and deemed resectable allowed unless tumor is more than 30 mm on CT scan

PATIENT CHARACTERISTICS:

Age

* Under 75

Performance status

* WHO 0-1

Life expectancy

* Not specified

Hematopoietic

* Granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* SGOT/SGPT ratio no greater than 1
* Albumin at least 35 g/L
* Total protein greater than 80%
* No liver cirrhosis with previous failure
* No ascites
* No jaundice
* No rupture of varicose esophageal veins
* No presence of varicose esophageal veins

Renal

* Creatinine no greater than 1.25 times normal

Cardiovascular

* Arterial O_2 greater than 60 mm Hg
* Arterial CO_2 no greater than 45 mm Hg
* No myocardial infarction within the past 6 months
* No progressive coronary artery disease grade 2 or greater
* No recent left ventricular failure
* No arterial disease stage II-IV

Pulmonary

* FEV_1 greater than 1 L/sec

Other

* Able to receive either study treatment
* No recurrent paralysis
* No weight loss greater than 10% from baseline
* No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* Not pregnant
* Fertile patients must use effective contraception during and for 3 months after completion of chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Primary outcomes:
measure: overal survival
timeFrame: 2010
Secondary outcomes:
measure: recurrence free survival
timeFrame: 2010
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Ghent
country: Belgium
facility: Universiteit Gent
city: Mons
country: Belgium
facility: CHR - Clinique Saint Joseph - Hopital de Warqueguies
city: Angers
country: France
facility: Centre Hospitalier Regional et Universitaire d'Angers
city: Angers
country: France
facility: Centre Paul Papin
city: Arras
country: France
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Boulogne Billancourt
country: France
facility: CHU Ambroise Pare
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Bourg En Bresse
country: France
facility: C.H. Bourg En Bresse
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier de Bourgoin - Jallieu
city: Brest
country: France
facility: CHU Brest - Hopital De La Cavale Blanche
city: Brive
country: France
facility: Centre Hospitalier General
city: Caen
country: France
facility: CHU de Caen
city: Chalon Sur Saone
country: France
facility: Clinique Sainte Marie
city: Clermont-Ferrand
country: France
facility: CHR Clermont Ferrand, Hotel dieu
city: Clichy
country: France
facility: Hopital Beaujon
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Compiegne
country: France
facility: Centre Hospitalier de Lagny
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de Dijon
city: Dunkerque
country: France
facility: Centre Hospitalier De Dunkerque - CHD
city: Evreux
country: France
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Libourne
country: France
facility: Hopital Robert Boulin
city: Lille
country: France
facility: Polyclinique Du Bois
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Centre Hospitalier Regional et Universitaire de Lille
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille Hopitaux Sud
city: Marseille
country: France
facility: CHU de la Timone
city: Maubeuge
country: France
facility: Centre Gray
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Meulan-en-Yvelines
country: France
facility: CH Meulan
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Mulhouse
country: France
facility: Centre Hospitalier
city: Nantes
country: France
facility: CHR Hotel Dieu
city: Nice
country: France
facility: Hopital de l'Archet
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Hopital Jean Bernard
city: Pontivy
country: France
facility: Centre Hospitalier De Pontivy
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: Centre Hospitalier Universitaire
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Germain-en-Laye
country: France
facility: Centre Hospitalier Intercommunal de Poissy
city: Saint Martin Boulogne
country: France
facility: Centre Joliot Curie Des Docteurs Jean-Christophe Chardon Jacques Hernandez Et Laurent Gasnault
city: Saint-Malo
country: France
facility: Centre Hospitalier General De Saint-Malo
city: Sainte-Clotilde
country: France
facility: Clinique Sainte Clotilde
city: Senlis
country: France
facility: C.H. Senlis
city: St. Esprit
country: France
facility: Centre Hospitalier D'Agen
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hopitaux Universitaire de Strasbourg
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Tours
country: France
facility: CHU de Tours
city: Valence
country: France
facility: Nouvelle Clinique Generale
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
city: Vandoeuvre-Les-Nancy
country: France
facility: CHU de Nancy - Hopitaux de Brabois
city: Vannes
country: France
facility: Centre d'Oncologie Saint-Yves
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
city: Erlangen
country: Germany
facility: Universitaet Erlangen
city: Freiburg
country: Germany
facility: Klinikum der Albert - Ludwigs - Universitaet Freiburg
city: Hamburg
country: Germany
facility: Universitaets-Krankenhaus Eppendorf
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
Study officials:
affiliation: Centre Hospitalier Regional et Universitaire de Lille
name: J. P. Triboulet
role: STUDY_CHAIR
affiliation: Institut Paoli-Calmettes
name: Jean-Francois Seitz, MD
role: STUDY_CHAIR
References:
citation: Mariette C, Robb WB, Piessen G. Reply to Letter: "The Role of Surgery for Patients With a Complete Clinical Response After Chemoradiation for Esophageal Cancer". Ann Surg. 2015 Dec;262(6):e101-2. doi: 10.1097/SLA.0000000000000668. No abstract available.
citation: Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014 Aug 10;32(23):2416-22. doi: 10.1200/JCO.2013.53.6532. Epub 2014 Jun 30.
citation: Robb WB, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF, Mariette C; Federation Francaise de Cancerologie Digestive, Societe Francaise de Radiotherapie Oncologique, Union des Centres de Lutte Contre le Cancer, Groupe Cooperateur Multidisciplinaire en Oncologie, French EsoGAstric Tumour working group, Federation de Recherche En Chirurgie. Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial. Ann Surg. 2015 May;261(5):902-8. doi: 10.1097/SLA.0000000000000991.
citation: Robb WB, Messager M, Dahan L, Mornex F, Maillard E, D'Journo XB, Triboulet JP, Bedenne L, Seitz JF, Mariette C; Federation Francophone de Cancerologie Digestive; Societe Francaise de Radiotherapie Oncologique; Union des Centres de Lutte Contre le Cancer; Groupe Cooperateur Multidisciplinaire en Oncologie; French EsoGAstric Tumour working group - Federation de Recherche En Chirurgie. Patterns of recurrence in early-stage oesophageal cancer after chemoradiotherapy and surgery compared with surgery alone. Br J Surg. 2016 Jan;103(1):117-25. doi: 10.1002/bjs.9959. Epub 2015 Oct 29.