Multimodal therapy (chemotherapy, radiation, surgery) with and without cetuximab, an additional anti-tumor agent, in patients with locally advanced esophageal carcinoma.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2009-016584-10-DE
• Date of registration: 14/04/2010
• Prospective Registration: Yes
• Primary sponsor: Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung SAKK
• Public title: Multimodal therapy (chemotherapy, radiation, surgery) with and without cetuximab, an additional anti-tumor agent, in patients with locally advanced esophageal carcinoma.
• 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: 02/08/2010
• Target sample size: 300
• Recruitment status: Not Recruiting
• 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 Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, Hungary, Switzerland

Contacts

• Name: Clinical Project Manager
• Affiliation: Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung SAKK

• Name: Clinical Project Manager
• Affiliation: Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung SAKK

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
Adequate coagulation profile: normal INR, PTT = 1.0 x ULN
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

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
Peritoneal carcinomatosis in case of adenocarcinomas infiltrating the gastric cardia (i.e. esophagogastric junction carcinoma Siewert type I or II)
Previous malignancies within five years or concomitant malignancies, except: nonmelanomatous 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, unstable angina pectoris, history of myocardial infarction within the last twelve 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 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.
MedDRA version: 20.0 Level: LLT Classification code 10041824 Term: Squamous cell carcinoma of esophagus System Organ Class: 100000004864
MedDRA version: 20.0 Level: LLT Classification code 10056092 Term: Adenocarcinoma of oesophagus System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

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)

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

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).

Timepoint(s) of evaluation of this end point: 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 from any cause

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 Outcome(s)

Secondary end point(s): · Progression-free survival after surgery (PFS-OP)
· Adverse events according to CTCAE version 4.0 and major postoperative complications
· Pathological remission (=TRG 1+2)
· R0-resection
· Overall survival
· Time to loco-regional failure after R0-resection
· Time to systemic failure after R0-resection
· Feasibility of the therapy: Completion of therapy
· In-hospital mortality
· Compliance with radiotherapy standards

Timepoint(s) of evaluation of this end point: Please refer to protocol section 13.

Secondary ID(s)

SAKK75/08

NCT01107639

Source(s) of Monetary Support

Merck KGaA, 64293 Darmstadt

SAKK

Ethics review

Status: Approved
Approval date:
Contact: