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

NCT01107639 | Completed Phase 3 DMC

• 4 other identifiers: SAKK 75/082009-016584-10EU-21024CDR0000669249
• Study Type: interventional
• Target: 297
• Locations: 5 countries
• Sites: 57

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.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Esophageal Cancer

Keywords

stage IIB esophageal cancer; adenocarcinoma of the esophagus; adenocarcinoma of the gastroesophageal junction; squamous cell carcinoma of the esophagus; stage IIIA esophageal cancer; stage IIIB esophageal cancer; stage IIIC esophageal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  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

  time from randomization to a defined event.

Secondary Outcomes (8)

• 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

Study Arms (2)

Additional immunotherapy (cetuximab)

EXPERIMENTAL

All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.

Biological: cetuximab; Drug: cisplatin; Drug: docetaxel; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy

Without additional immunotherapy

ACTIVE COMPARATOR

Standard therapy without immunotherapy (cetuximab).

Drug: cisplatin; Drug: docetaxel

Interventions

cetuximab BIOLOGICAL

Loading dose 400 mg/m2 2h infusion Weekly: 250 mg/m2 1h infusion

Also known as: Erbitux

Additional immunotherapy (cetuximab)

cisplatin DRUG

* Cisplatin 75 mg/m2 1h infusion d1, 22 * Cisplatin 25 mg/m2 1h infusion weekly x5

Additional immunotherapy (cetuximab); Without additional immunotherapy

docetaxel DRUG

* Docetaxel 75 mg/m2 1h infusion d1, 22 * Docetaxel 20 mg/m2 1/2h infusion weekly x5

Also known as: Taxotere or generic product

Additional immunotherapy (cetuximab); Without additional immunotherapy

adjuvant therapy PROCEDURE

During the adjuvant phase, all infusions, given every two weeks, will be at a dose of 500mg/m².

Additional immunotherapy (cetuximab)

neoadjuvant therapy PROCEDURE

During the neoadjuvant phase, the first infusion of cetuximab should be at a dose of 400 mg/m² administered over a period of 2 hours and all subsequent infusions, given weekly, should be of 250 mg/m² over a period of 1 hour, unless any infusion related reaction was observed at a previous infusion. (The maximum infusion rate is 10 mg/min, corresponding to 2 mL/min ready-to-use solution.

Additional immunotherapy (cetuximab)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed esophageal carcinoma * Meets the following criteria: * Resectable, locally advanced disease as determined by the combination of CT scan, endoluminal ultrasound (EUS), PET scan, and a multidisciplinary team discussion * T2, N1-3; T3, any N; or T4a, any N (if technically resectable with curative intent \[R0\] as decided by a multidisciplinary team discussion) * EUS-guided fine-needle aspiration (FNA) allowed, but determines nodal status only if positive FNA * No T1, any N, M0; or T2, N0, M0; T4a (due to infiltration of the trachea-bronchial tree or organ involvement that cannot be operated on with curative intent \[R0\] as decided by a multidisciplinary team discussion); T4b; or distant metastasis (M1) * Type I or II disease according to the Siewert classification * Squamous cell carcinoma (including basaloid-squamous cell and adenosquamous carcinoma) or adenocarcinoma of the thoracic esophagus or the esophagogastric junction (from 5 cm below the entrance of the esophagus into the thorax to the gastric cardia) * Patients with obstructive tumors are eligible (obstructive tumors will be considered as locally advanced tumors) * No cervical esophageal carcinoma and tumors involving the first 5 cm of the thoracic esophagus * No airway infiltration in case of tumors at or above the tracheal bifurcation * No peritoneal carcinomatosis in case of adenocarcinomas infiltrating the gastric cardia (i.e., esophagogastric junction carcinoma Siewert type I or II) PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Neutrophil count ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Creatinine clearance \> 60 mL/min * Bilirubin ≤ 1.0 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * AST ≤ 1.5 times ULN * INR normal * PTT ≤ 1.0 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 12 months after completion of study therapy * FEV\_1 ≥ 1.5 L OR ≥ 75% of the reference value * Must be compliant and geographically proximal for staging and follow-up * Considered operable (i.e., appropriate organ functions and ability to undergo general anesthesia) * No other malignancies within the past 5 years except nonmelanomatous skin cancer or adequately treated carcinoma in situ of the cervix * No severe or uncontrolled cardiovascular disease, including any of the following: * NYHA class III-IV congestive heart failure * Unstable angina pectoris * Myocardial infarction within the past 12 months * Significant arrhythmias * No psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, and answering questionnaires * No active uncontrolled infection * No serious underlying medical condition that, in the opinion of the investigator, could impair the ability of the patient to participate in the trial (e.g., uncontrolled diabetes mellitus or active autoimmune disease) * No preexisting peripheral neuropathy \> grade 1 * No definite contraindications for the use of corticosteroids and antihistamines as premedication * No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs PRIOR CONCURRENT THERAPY: * No prior chemotherapy or radiotherapy to the chest * At least 30 days since prior treatment in another clinical trial * No concurrent drugs contraindicated for use with the trial drugs * No other concurrent anticancer treatments * No other concurrent experimental drugs or investigational treatments

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (57)

Landeskrankenhaus

Feldkirch, A-6807, Austria

Location

Universitätsklinik für Innere Medizin I

Innsbruck, A-6020, Austria

Location

Krankenhaus Barmherzige Schwestern Linz

Linz, A-4010, Austria

Location

Krankenhaus der Elisabethinen Linz GmbH

Linz, A-4010, Austria

Location

Universitätsklinikum der PMU Salzburg

Salzburg, A-5020, Austria

Location

Universitätsklinik für Innere Medizin

Vienna, 1090, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, A-4600, Austria

Location

Centre Hospitalier Général

Béziers, 34525, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

Hôtel Dieu Estaing

Clermont-Ferrand, 63003, France

Location

Centre Georges-François Leclerc

Dijon, 21079, France

Location

CHU Le Bocage

Dijon, 21079, France

Location

Centre Bourgogne

Lille, 59000, France

Location

CHRU de Lille

Lille, 59037, France

Location

Clinique François Chénieux

Limoges, 87000, France

Location

CHU la TIMONE

Marseille, 13385, France

Location

CH Régional de la Source

Orléans, 45067, France

Location

CH Saint Jean

Perpignan, 66046, France

Location

Hôpital Haut Leveque

Pessac, 33604, France

Location

CHU

Rennes, 35033, France

Location

CHU de Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez, 42277, France

Location

Clinique Ste Anne

Strasbourg, 67000, France

Location

Hôpital Purpan

Toulouse, 31509, France

Location

Charite University Hospital - Campus Virchow Klinikum

Berlin, D-13353, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, D-40225, Germany

Location

Kliniken Essen - Mitte

Essen, D-45136, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, D-79106, Germany

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, 74078, Germany

Location

Klinikum Herford

Herford, D-32049, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, D-71640, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH

Marburg, D-35043, Germany

Location

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, D-81377, Germany

Location

Staedtisches Klinikum Solingen

Solingen, D-42653, Germany

Location

Klinikum Stuttgart - Katharinenhospital

Stuttgart, 70174, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, D-72076, Germany

Location

Szent Laszlo Korhaz

Budapest, 1097, Hungary

Location

Hirslanden Klinik Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

St. Claraspital AG

Basel, CH-4016, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hôpital du Valais (RSV)-CHCVs

Sion, 1951, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Ospedale Italiano

Viganello, CH-6962, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

Onkozentrum Klinik im Park

Zurich, 8038, Switzerland

Location

Klinik Hirslanden

Zurich, CH-8032, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (3)

• Ruhstaller T, Thuss-Patience P, Hayoz S, Schacher S, Knorrenschild JR, Schnider A, Plasswilm L, Budach W, Eisterer W, Hawle H, Mariette C, Hess V, Mingrone W, Montemurro M, Girschikofsky M, Schmidt SC, Bitzer M, Bedenne L, Brauchli P, Stahl M; Swiss Group for Clinical Cancer Research (SAKK); German Esophageal Cancer Study Group; Austrian 'Arbeitsgemeinschaft Medikamentose Tumortherapie' (AGMT); Federation Francophone de Cancerologie Digestive (FFCD)/Federation de Recherche en Chirurgie (FRENCH). Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08). Ann Oncol. 2018 Jun 1;29(6):1386-1393. doi: 10.1093/annonc/mdy105.

  PMID: 29635438 RESULT

• von Holzen U, Schmidt S, Hayoz S, Steffen T, Grieder F, Bartsch D, Schnider A, Knoefel WT, Piessen G, Kettelhack C, Marti WR, Schafer M, Fugger R, Koigsrainer A, Gloor B, Furrer M, Gerard MA, Hawle H, Walz MK, Alesina P, Ruhstaller T; Swiss Group for Clinical Cancer Research (SAKK), the German Esophageal Cancer Study Group, the Austrian Arbeitsgemeinschaft Medikamentose Tumortherapie (AGMT), the Federation Francophone de Cancerologie Digestive (FFCD)/Federation de Recherche en Chirurgie (FRENCH). Surgical Outcomes After Neoadjuvant Chemoradiation Followed by Curative Surgery in Patients With Esophageal Cancer: An Intergroup Phase III Trial of the Swiss Group for Clinical Cancer Research (SAKK 75/08). Ann Surg. 2022 Jun 1;275(6):1130-1136. doi: 10.1097/SLA.0000000000004334. Epub 2020 Aug 26.

  PMID: 33055589 DERIVED

• Fehr M, Hawle H, Hayoz S, Thuss-Patience P, Schacher S, Riera Knorrenschild J, Durr D, Knoefel WT, Rumpold H, Bitzer M, Zweifel M, Samaras P, Mey U, Kung M, Winterhalder R, Eisterer W, Hess V, Gerard MA, Templeton A, Stahl M, Ruhstaller T; Swiss Group for Clinical Cancer Research (SAKK); German Esophageal Cancer Study Group; Austrian Arbeitsgemeinschaft Medikamentose Tumortherapie (AGMT); Federation Francophone de Cancerologie Digestive (FFCD) / Federation de Recherche en Chirurgie (FRENCH). High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08. BMC Cancer. 2020 Feb 28;20(1):166. doi: 10.1186/s12885-020-6623-z.

  PMID: 32111181 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Interventions

Cetuximab; Cisplatin; Docetaxel; Chemotherapy, Adjuvant; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Thomas Ruhstaller, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Michael Stahl, MD

  Kliniken Essen-Mitte

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2010
• First Posted: April 21, 2010
• Study Start: May 27, 2010
• Primary Completion: October 6, 2016
• Study Completion: December 9, 2018
• Last Updated: October 20, 2020

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (21); DE (12); HU (1); AU (7); FR (16)