E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable locally advanced esophageal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable locally advanced esophageal cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015362 |
E.1.2 | Term | Esophageal cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030151 |
E.1.2 | Term | Oesophageal cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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E.2.2 | Secondary objectives of the trial |
1-year overall survival 1-year and 2-year progression-free survival 1-year and 2-year loco-regional control 1-year and 2-year metastases-free survival Toxicity (NCI-CTC 4.0) Overall response rate (RECIST Version 1.1) Quality of Life (EORTC QLQ-C30 and QLQ OES18)
In addition the following parameters will be assessed irrespective of a specific time point: • OS • PFS • MFS
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed written informed consent • Male or female between 18 and 75 years; patients > 75 years if KPS ≥ 80 • Histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus, which is not curatively resectable • KPS ≥ 70 • Women of child-bearing potential must have a negative pregnancy test • Adequate cardiac, pulmonary, and ear function • Adequate bone marrow function: leucocytes > 3.0 x 109/L, neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, hemoglobin > 10.0 g/dL • Adequate liver function: Bilirubin < 2.0 mg/dL, SGOT, SGPT, AP, -GT < 3 x ULN • Adequate renal function: serum creatinine < 1.5 mg/dL, creatinine clearance > 50 ml/min (calculated value according to Cockroft-Gault equation) • No known allergy against chimeric antibodies • Effective contraception for both male and female patients if the risk of conception exists
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E.4 | Principal exclusion criteria |
• Distant metastasis (M1b) • Previous treatment of esophageal cancer • Previous exposure to monoclonal antibodies and / or EGFR-targeted therapy • Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix • Serious concomitant disease or medical condition • FEV1 < 1,1 • Clinically relevant coronary artery disease or a history of myocardial infarction within the last 12 months or left ventricular ejection fraction (LVEF) below the institutional range of normal • Any active dermatological condition > Grade 1 • Contraindications to receive cisplatin, 5-FU or cetuximab • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening • Pregnancy or lactation • Known active drug abuse/alcohol abuse • Social situations limiting the compliance with the study requirements
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E.5 End points |
E.5.1 | Primary end point(s) |
2-year overall survival (rate) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 years after start of treatment |
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E.5.2 | Secondary end point(s) |
[1] 1-year OS (rate) [2]-year and 2-year PFS (rate) [3] 1-year and 2-year LC (rate) [41] 1-year and 2-year MFS (rate) [5] OS, PFS, MFS
Overall response rate Toxicity
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
[1-4] 1 and 2 years after start of treatment, respectively [5] irrespective of a specific time point until 2 years after start of treatment of last patient
Response rate and toxicity up to end of treatment evaluation (i.e. 16 weeks) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
background radiochemotherapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Recuitment will be stopped on 31.12.2016. The end of study is reached when the last patient has completed the 2-year Follow-up period, therefore, the latest possible date will be 31.12.2018 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |