Multimodal therapy with and without cetuximab in patients with locally advanced esophageal carcinoma. An open-label phase III trial

• Register: EUCTR
• Last refreshed on: 2 October 2012
• Main ID: EUCTR2009-016584-10-HU
• Date of registration: 28/05/2010
• Prospective Registration: Yes
• Primary sponsor: Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung SAKK
• Public title: Multimodal therapy with and without cetuximab in patients with locally advanced esophageal carcinoma. An open-label phase III trial
• Scientific title: Multimodal therapy with and without cetuximab in patients with locally advanced esophageal carcinoma. An open-label phase III trial
• Date of first enrolment: 08/07/2010
• Target sample size: 300
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016584-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard therapy w/o IMP

Countries of recruitment

Austria, Germany, Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
Histologically confirmed 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 (=esophagogastric junction), types I and II according to the Siewert staging system).
Resectable, locally advanced disease (the stage is determined by the combination of CT scan, EUS and PET and by a multidisciplinary team discussion)
Age: 18-75 years
Health status: WHO performance status (PS) = 1
Patient is considered operable (appropriate organ functions)
Adequate renal function: creatinine clearance > 60 mL/min, calculated according to the formula of Cockroft-Gault
Adequate pulmonary function: FEV1 > 1.5L or, if < 1.5L at least 75% of the reference value
Adequate hepatic function: bilirubin = 1.0 x ULN, AP = 2.5 x ULN, AST = 1.5 x ULN
Adequate hematologic values: neutrophils = 1.5 x 109/L, platelets = 100 x 109/L
Patient compliance and geographic proximity allow proper staging and follow-up.
Women are not breastfeeding, are using effective contraception if sexually active, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter.
Men agree not to father a child during participation in the trial and during the twelve months thereafter.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Stage T1 Nany M0
Stage T2 N0 M0
Stage T4a due to infiltration of the tracheo-bronchial tree or organ involvement which cannot be operated on with curative intent (R0) as decided by a multidisciplinary team discussion
Stage T4b
Distant metastasis (M1)
Cervical esophageal carcinoma and tumors involving the first 5 cm of the thoracic esophagus
Airway infiltration in case of tumors at or above the tracheal bifurcation
Previous malignancies within five years or concomitant malignancies, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer
Prior chemotherapy or prior RT to the chest
Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV (see Appendix 5), unstable angina pectoris, history of myocardial infarction within the last three months, significant arrhythmias)
Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent and answering the questions of the EQ-5D questionnaire and HEA forms (EQ-5D questionnaire and HEA forms applicable for Swiss and German centers and for patients who gave consent for the HEA only)
Active uncontrolled infection
Serious underlying medical condition (judged by the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled diabetes mellitus, active autoimmune disease)
Preexisting peripheral neuropathy (> grade 1)
Concurrent treatment with other experimental drugs or other anti-cancer therapy; treatment in a clinical trial within 30 days prior to trial entry
Definite contraindications for the use of corticosteroids and antihistamines as premedication
Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs
Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally advanced esophageal carcinoma.

Intervention(s)

Trade Name: Erbitux
Product Name: Cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923564
Current Sponsor code: Merck
Other descriptive name: Erbitux
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: Determine the efficacy of neoadjuvant radiochemotherapy (RCT) combined with immunotherapy followed by adjuvant immunotherapy compared with the same schedule without immunotherapy (neoadjuvant and adjuvant).

Primary end point(s): Progression-free survival (PFS)

Secondary Objective: Compare the toxicity of the two therapy arms and determine patterns of failure overall and with regard to histology; further to evaluate economic aspects in a subproject and to perform a radiotherapy quality assurance program.

Secondary ID(s)

2009-016584-10-DE

SAKK 75/08