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Adenocarcinoma of the Gastroesophageal JunctionPhase 3NCT01107639

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

A Phase 3 study testing cetuximab, cisplatin and docetaxel in people with Adenocarcinoma of the Gastroesophageal Junction and Esophageal Cancer, run by Swiss Cancer Institute at 57 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
cetuximab, cisplatin and docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
297 participants
Where
57 sitesin 5 countries
Study dates
27 May 2010to 9 Dec 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

57 sites in 5 countries.

57 sites in 5 countries

Switzerland21 sites

  • Hirslanden Klinik Aarau

    Aarau, CH-5001

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Kantonsspital Baden

    Baden, CH-5404

  • St. Claraspital AG

    Basel, CH-4016

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Inselspital Bern

    Bern, CH-3010

  • Kantonsspital Bruderholz

    Bruderholz, CH-4101

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • Hopital Cantonal Universitaire de Geneve

    Geneva, CH-1211

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Kantonsspital Liestal

    Liestal, CH-4410

  • Kantonsspital Olten

    Olten, CH-4600

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • Hôpital du Valais (RSV)-CHCVs

    Sion, 1951

  • Regionalspital

    Thun, 3600

  • Ospedale Italiano

    Viganello, CH-6962

  • Kantonsspital Winterthur

    Winterthur, CH-8400

  • Onkozentrum Klinik im Park

    Zurich, 8038

  • Klinik Hirslanden

    Zurich, CH-8032

  • City Hospital Triemli

    Zurich, CH-8063

  • UniversitaetsSpital Zuerich

    Zurich, CH-8091

Other trials in Switzerland

France16 sites

  • Centre Hospitalier Général

    Béziers, 34525

  • Hôpital Avicenne

    Bobigny, 93000

  • Hôtel Dieu Estaing

    Clermont-Ferrand, 63003

  • Centre Georges-François Leclerc

    Dijon, 21079

  • CHU Le Bocage

    Dijon, 21079

  • Centre Bourgogne

    Lille, 59000

  • CHRU de Lille

    Lille, 59037

  • Clinique François Chénieux

    Limoges, 87000

  • CHU la TIMONE

    Marseille, 13385

  • CH Régional de la Source

    Orléans, 45067

  • CH Saint Jean

    Perpignan, 66046

  • Hôpital Haut Leveque

    Pessac, 33604

  • CHU

    Rennes, 35033

  • CHU de Saint Etienne - Hôpital Nord

    Saint-Priest-en-Jarez, 42277

  • Clinique Ste Anne

    Strasbourg, 67000

  • Hôpital Purpan

    Toulouse, 31509

Other trials in France

Germany12 sites

  • Charite University Hospital - Campus Virchow Klinikum

    Berlin, D-13353

  • Universitaetsklinikum Duesseldorf

    Düsseldorf, D-40225

  • Kliniken Essen - Mitte

    Essen, D-45136

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, D-79106

  • SLK-Kliniken Heilbronn GmbH

    Heilbronn, 74078

  • Klinikum Herford

    Herford, D-32049

  • Klinikum Ludwigsburg

    Ludwigsburg, D-71640

  • Universitaetsklinikum Giessen und Marburg GmbH

    Marburg, D-35043

  • Klinikum der Universitaet Muenchen - Grosshadern Campus

    Munich, D-81377

  • Staedtisches Klinikum Solingen

    Solingen, D-42653

  • Klinikum Stuttgart - Katharinenhospital

    Stuttgart, 70174

  • Universitaetsklinikum Tuebingen

    Tübingen, D-72076

Other trials in Germany

Austria7 sites

  • Landeskrankenhaus

    Feldkirch, A-6807

  • Universitätsklinik für Innere Medizin I

    Innsbruck, A-6020

  • Krankenhaus Barmherzige Schwestern Linz

    Linz, A-4010

  • Krankenhaus der Elisabethinen Linz GmbH

    Linz, A-4010

  • Universitätsklinikum der PMU Salzburg

    Salzburg, A-5020

  • Universitätsklinik für Innere Medizin

    Vienna, 1090

  • Klinikum Wels-Grieskirchen GmbH

    Wels, A-4600

Other trials in Austria

Hungary1 site

  • Szent Laszlo Korhaz

    Budapest, 1097

Other trials in Hungary

About this study

Official title: Multimodal Therapy With and Without Cetuximab in Patients With Locally Advanced Esophageal Carcinoma - An Open-Label Phase III Trial

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.

Read the 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.

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
Medical subject headings
Esophageal Neoplasms, Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cetuximabBiological

    Also called Erbitux

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

  • cisplatinDrug

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

  • docetaxelDrug

    Also called Taxotere or generic product

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

  • adjuvant therapyProcedure or surgery

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

  • neoadjuvant therapyProcedure or surgery

    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.

Study groups in NCT01107639
Study groupRoleWhat they receive
Additional immunotherapy (cetuximab)ExperimentalAll patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Receives: Biological: cetuximab; Drug: cisplatin; Drug: docetaxel; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy
Without additional immunotherapyActive comparatorStandard therapy without immunotherapy (cetuximab).
Receives: Drug: cisplatin; Drug: docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: time from randomization to a defined event.

Secondary outcomes (8)

  1. Progression-free survival after surgery

    Measured: from date of surgery to an event as defined in PFS.

  2. Adverse events according to CTCAE version 4.0 and major postoperative complications

    Measured: during treatment and follow-up period.

  3. Pathological remission

    Measured: Assessed according to the tumor regression model of Mandard

  4. Overall survival

    Measured: time from trial randomization to the date of death from any cause

  5. Time to locoregional failure after R0 resection

    Measured: from date of surgery to date of first documented loco-regional failure

  6. Time to systemic failure after R0 resection

    Measured: from date of surgery to date of first documented systemic failure

  7. In-hospital mortality

    Measured: occurring after surgery but while the patient remains in hospital

  8. Time to progression (TTP)

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2010 (estimated)
  2. Study start27 May 2010
  3. Primary completion6 Oct 2016
  4. Study completion9 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
297 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01107639
Sponsor's protocol ID
SAKK 75/08
Other IDs
2009-016584-10, EU-21024, CDR0000669249, 2009
Status last verified
May 2019
First submitted
20 Apr 2010
Last updated
20 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29635438

  • 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.

    PubMed 33055589

  • 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.

    PubMed 32111181

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cetuximab, cisplatin and docetaxel in people with Adenocarcinoma of the Gastroesophageal Junction and Esophageal Cancer, run by Swiss Cancer Institute at 57 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in Switzerland, France, Germany, Austria, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: time from randomization to a defined event.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01107639, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2020.

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