Surgery With or Without Radiation Therapy and Chemotherapy in Treating Patients With Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

Randomized Study of Pre-Operative Radio-Chemotherapy Versus Surgery Alone in Thoracic Esophageal Cancer Deemed to be Resectable

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047112
• Other study ID #: CDR0000257600
• Secondary ID: FFCD-9901EORTC-2
• Status: Completed
• Phase: Phase 3
• Start date: May 2002
• Est. completion date: September 2010

Study information

• Verified date: March 2020
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• cisplatin

• fluorouracil

Procedure:
• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Universiteit Gent	Ghent
Belgium	CHR - Clinique Saint Joseph - Hopital de Warqueguies	Mons
France	Centre Hospitalier Regional et Universitaire d'Angers	Angers
France	Centre Paul Papin	Angers
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	CHU Ambroise Pare	Boulogne Billancourt
France	Centre Hospitalier Docteur Duchenne	Boulogne Sur Mer
France	C.H. Bourg En Bresse	Bourg En Bresse
France	Centre Hospitalier de Bourgoin - Jallieu	Bourgoin-Jallieu
France	CHU Brest - Hopital De La Cavale Blanche	Brest
France	Centre Hospitalier General	Brive
France	CHU de Caen	Caen
France	Clinique Sainte Marie	Chalon Sur Saone
France	CHR Clermont Ferrand, Hotel dieu	Clermont-Ferrand
France	Hopital Beaujon	Clichy
France	Hopital Louis Pasteur	Colmar
France	Centre Hospitalier de Lagny	Compiegne
France	Centre Hospitalier Universitaire de Dijon	Dijon
France	Centre Hospitalier De Dunkerque - CHD	Dunkerque
France	Centre Hospitalier Departemental	La Roche Sur Yon
France	Hopital Andre Mignot	Le Chesnay
France	Centre Jean Bernard	Le Mans
France	Hopital Robert Boulin	Libourne
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Centre Oscar Lambret	Lille
France	Polyclinique Du Bois	Lille
France	Hopital de la Croix Rousse	Lyon
France	Assistance Publique Hopitaux de Marseille Hopitaux Sud	Marseille
France	CHU de la Timone	Marseille
France	Institut J. Paoli and I. Calmettes	Marseille
France	Centre Gray	Maubeuge
France	Centre Hospitalier de Meaux	Meaux
France	Hopital Notre-Dame de Bon Secours	Metz
France	CH Meulan	Meulan-en-Yvelines
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre Hospitalier	Mulhouse
France	CHR Hotel Dieu	Nantes
France	Hopital de l'Archet	Nice
France	CHR D'Orleans - Hopital de la Source	Orleans
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Saint Antoine	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Hopital Jean Bernard	Poitiers
France	Centre Hospitalier De Pontivy	Pontivy
France	Centre Hospitalier Universitaire	Reims
France	Institut Jean Godinot	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Rene Huguenin	Saint Cloud
France	Centre Hospitalier Intercommunal de Poissy	Saint Germain-en-Laye
France	Centre Joliot Curie Des Docteurs Jean-Christophe Chardon Jacques Hernandez Et Laurent Gasnault	Saint Martin Boulogne
France	Centre Hospitalier General De Saint-Malo	Saint-Malo
France	Clinique Sainte Clotilde	Sainte-Clotilde
France	C.H. Senlis	Senlis
France	Centre Hospitalier D'Agen	St. Esprit
France	Centre Paul Strauss	Strasbourg
France	Hopital Universitaire Hautepierre	Strasbourg
France	Hopitaux Universitaire de Strasbourg	Strasbourg
France	CHU de Tours	Tours
France	Nouvelle Clinique Generale	Valence
France	Centre Hospitalier de Valenciennes	Valenciennes
France	CHU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy
France	Centre d'Oncologie Saint-Yves	Vannes
France	Institut Gustave Roussy	Villejuif
Germany	Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch	Berlin
Germany	Universitaet Erlangen	Erlangen
Germany	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg
Germany	Universitaets-Krankenhaus Eppendorf	Hamburg
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht

Sponsors (5)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive	European Organisation for Research and Treatment of Cancer - EORTC, GERCOR - Multidisciplinary Oncology Cooperative Group, Societe Francaise de Radiotherapie Oncologique, UNICANCER

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Netherlands, 

References & Publications (4)

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 can — View 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. — View Citation

Mariette C, Seitz JF, Maillard E, et al.: Surgery alone versus chemoradiotherapy followed by surgery for localized esophageal cancer: analysis of a randomized controlled phase III trial FFCD 9901. [Abstract] J Clin Oncol 28 (Suppl 15): A-4005, 2010.

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; Fédération Française de Cancérologie Digestive, Société Française de Radiothérapie Oncologiq — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overal survival		2010
Secondary	recurrence free survival		2010