Radiation Therapy and Chemotherapy, With or Without Cetuximab, Followed by Surgery in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed by Surgery

Phase 3

Completed

• Conditions: Adenocarcinoma of the Gastroesophageal Junction; Esophageal Cancer
• Interventions: Biological: cetuximab; Drug: cisplatin; Drug: docetaxel; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy

• Registration Number: NCT01107639
• Lead Sponsor: Swiss Group for Clinical Cancer Research

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays and to kill tumor cells. Drugs used in chemotherapy, such as docetaxel 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. It is not yet known whether giving radiation therapy together with chemotherapy is more effective with or without cetuximab in treating patients with esophageal cancer.

PURPOSE: This randomized phase III trial is studying giving radiation therapy together with chemotherapy, with or without cetuximab, followed by surgery in treating patients with locally advanced esophageal cancer that can be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

* To determine the efficacy of neoadjuvant radiochemotherapy comprising docetaxel, cisplatin, and radiotherapy in combination with cetuximab followed by surgery and adjuvant cetuximab versus neoadjuvant radiochemotherapy comprising docetaxel, cisplatin, and radiotherapy followed by surgery in patients with locally advanced esophageal carcinoma.

Secondary

* To compare the toxicity of the two therapy arms.

* To determine patterns of failure overall and with regard to histology.

* To evaluate economic aspects in a subproject and to perform a radiotherapy quality assurance program.

OUTLINE: This is a multicenter study. Patients are stratified according to center, histology (adenocarcinoma vs squamous cell carcinoma), primary tumor (T2 vs T3-4), and gender (male vs female). Patients are randomized to 1 of 2 treatment arms.

* Arm A:

* Induction chemotherapy (docetaxel and cisplatin) and concurrent cetuximab Patients receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and cetuximab IV over 1-2 hours on day 1, 8, and 15. Treatment repeats every 21 days for 2 courses.

* Chemotherapy (docetaxel and cisplatin), cetuximab, and concurrent radiotherapy Beginning in week 7, patients receive cetuximab IV over 1 hour, docetaxel IV over 30 minutes, cisplatin IV over 1 hour on days 43, 50, 57, 64, and 71 and undergo radiotherapy 5 days a week for 5 weeks. Patients then undergo surgery 4-7 weeks after completion of radiotherapy.

* Adjuvant cetuximab Beginning 3-6 weeks after completion of surgery, patients receive cetuximab IV over 1-2 hours once every 2 weeks for a total of 6 doses.

* Arm B: Patients receive induction chemotherapy comprising docetaxel IV and cisplatin IV for 2 courses as in arm A. Beginning in week 7, patients receive docetaxel IV, cisplatin IV, and concurrent radiotherapy for 5 weeks as in arm A. Patients then undergo surgery 4-7 weeks after completion of radiotherapy.

After completion of study therapy, patients are followed up at 1 (arm B) or 6 (arm A) months, every 3 months for 3 years, and then every 6 months for 2 years.

Study Timeline

• Study First Submitted: 2010-04-20
• Study First Submitted QC: 2010-04-20
• Study First Posted: 2010-04-21
• Study Start: 2010-05-27
• Primary Completion: 2016-10-06
• Study Completion: 2018-12-09
• Status Verified: 2019-05
• Last Update Submitted: 2020-10-19
• Last Update Posted: 2020-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 297

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Additional immunotherapy (cetuximab)	cetuximab	All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Additional immunotherapy (cetuximab)	neoadjuvant therapy	All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Additional immunotherapy (cetuximab)	docetaxel	All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Additional immunotherapy (cetuximab)	adjuvant therapy	All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Without additional immunotherapy	docetaxel	Standard therapy without immunotherapy (cetuximab).
Additional immunotherapy (cetuximab)	cisplatin	All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Without additional immunotherapy	cisplatin	Standard therapy without immunotherapy (cetuximab).

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	time from randomization to a defined event.	time from randomization to one of the following events, whichever comes first: * Tumor progression at any time (progression of primary tumor or local lymph nodes, appearance of new lesions); * Recurrence at local, regional or distant site after surgery; * Death from any cause

Secondary Outcome Measures

Name	Time	Method
Progression-free survival after surgery	from date of surgery to an event as defined in PFS.
Adverse events according to CTCAE version 4.0 and major postoperative complications	during treatment and follow-up period.
Pathological remission	Assessed according to the tumor regression model of Mandard
Overall survival	time from trial randomization to the date of death from any cause
Time to locoregional failure after R0 resection	from date of surgery to date of first documented loco-regional failure
Time to systemic failure after R0 resection	from date of surgery to date of first documented systemic failure
In-hospital mortality	occurring after surgery but while the patient remains in hospital
Time to progression (TTP)	Time to progression is defined as time from randomization to one of the following events, whichever comes first: - Tumor progression at any time. - Recurrence at local, regional or distant site after surgery. - Death due to tumor

Trial Locations

Locations (57)

Hôpital du Valais (RSV)-CHCVs; 🇨🇭 Sion, Switzerland

Kantonsspital Winterthur; 🇨🇭 Winterthur, Switzerland

City Hospital Triemli; 🇨🇭 Zurich, Switzerland

Landeskrankenhaus; 🇦🇹 Feldkirch, Austria

Krankenhaus Barmherzige Schwestern Linz; 🇦🇹 Linz, Austria

Krankenhaus der Elisabethinen Linz GmbH; 🇦🇹 Linz, Austria

Universitätsklinikum der PMU Salzburg; 🇦🇹 Salzburg, Austria

CHRU de Lille; 🇫🇷 Lille, France

Clinique François Chénieux; 🇫🇷 Limoges, France

Centre Bourgogne; 🇫🇷 Lille, France

Universitaetsklinikum Giessen und Marburg GmbH; 🇩🇪 Marburg, Germany

Charite University Hospital - Campus Virchow Klinikum; 🇩🇪 Berlin, Germany

Staedtisches Klinikum Solingen; 🇩🇪 Solingen, Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus; 🇩🇪 Munich, Germany

Klinikum Stuttgart - Katharinenhospital; 🇩🇪 Stuttgart, Germany

Universitaetsklinikum Tuebingen; 🇩🇪 Tuebingen, Germany

Szent Laszlo Korhaz; 🇭🇺 Budapest, Hungary

Inselspital Bern; 🇨🇭 Bern, Switzerland

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Kantonsspital - St. Gallen; 🇨🇭 St. Gallen, Switzerland

Onkozentrum Klinik im Park; 🇨🇭 Zurich, Switzerland

CH Saint Jean; 🇫🇷 Perpignan Cedex, France

CHU; 🇫🇷 Rennes Cedex 9, France

Universitätsklinik für Innere Medizin I; 🇦🇹 Innsbruck, Austria

Klinikum Wels-Grieskirchen GmbH; 🇦🇹 Wels, Austria

Universitätsklinik für Innere Medizin; 🇦🇹 Wien, Austria

Hôpital Avicenne; 🇫🇷 Bobigny, France

Centre Hospitalier Général; 🇫🇷 Béziers, France

Hôtel Dieu Estaing; 🇫🇷 Clermont Ferrand, France

Centre Georges-François Leclerc; 🇫🇷 Dijon, France

CH Régional de la Source; 🇫🇷 Orleans, France

Universitaetsklinikum Duesseldorf; 🇩🇪 Duesseldorf, Germany

Hôpital Purpan; 🇫🇷 Toulouse, France

CHU Le Bocage; 🇫🇷 Dijon Cedex, France

Clinique Ste Anne; 🇫🇷 Strasbourg, France

CHU la TIMONE; 🇫🇷 Marseille, France

Hôpital Haut Leveque; 🇫🇷 Pessac Cedex, France

CHU de Saint Etienne - Hôpital Nord; 🇫🇷 St Priest En Jarez, France

SLK-Kliniken Heilbronn GmbH; 🇩🇪 Heilbronn, Germany

Klinikum Herford; 🇩🇪 Herford, Germany

Klinikum Ludwigsburg; 🇩🇪 Ludwigsburg, Germany

Hirslanden Klinik Aarau; 🇨🇭 Aarau, Switzerland

Kantonsspital Aarau; 🇨🇭 Aarau, Switzerland

Kantonsspital Baden; 🇨🇭 Baden, Switzerland

St. Claraspital AG; 🇨🇭 Basel, Switzerland

Regionalspital; 🇨🇭 Thun, Switzerland

Klinik Hirslanden; 🇨🇭 Zurich, Switzerland

Universitaetsspital-Basel; 🇨🇭 Basel, Switzerland

Kantonsspital Bruderholz; 🇨🇭 Bruderholz, Switzerland

Kantonsspital Graubuenden; 🇨🇭 Chur, Switzerland

Hopital Cantonal Universitaire de Geneve; 🇨🇭 Geneva, Switzerland

Kantonsspital Liestal; 🇨🇭 Liestal, Switzerland

Kantonsspital Olten; 🇨🇭 Olten, Switzerland

UniversitaetsSpital Zuerich; 🇨🇭 Zurich, Switzerland

Ospedale Italiano; 🇨🇭 Viganello, Switzerland

Kliniken Essen - Mitte; 🇩🇪 Essen, Germany

Universitaetsklinikum Freiburg; 🇩🇪 Freiburg, Germany