E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Esophago-gastric adenocarcinoma |
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MedDRA Classification |
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 |
The primary objective of this study is to determine the response rates of matuzumab in combination with ECX as background chemotherapy and of ECX alone in subjects with metastatic esophago-gastric cancer. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess the following parameters: • Response duration • Median time to tumor progression • Median survival time • Safety and tolerability • Quality of life • Protein biomarkers In addition, the following parameters will be assessed for subjects receiving matuzumab • Determination of HAHA • Matuzumab peak and trough values
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Written informed consent provided prior to any prescreening procedure 2. Male or female, 18 years or older 3. Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the lower third of the esophagus 4. Metastatic disease 5. Normal cardiac function (left ventricular ejection fraction within the institutional normal range) 6. At least 1 measurable lesion according to the modified WHO criteria as defined in Section 7.2.2. 7. Archived tissue available for EGFR testing and immunohistochemical evidence of tumor EGFR (HER-1) expression in the most recent available sample 8. ECOG (Eastern Cooperative Oncology Group) performance status 0-1 9. Life-expectancy > 12 weeks 10. Adequate liver, bone marrow, and renal function, defined as: • Bilirubin < 1.5 x upper limit of normal (ULN) • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x ULN (for subjects with liver metastases ALT/AST < 5 x ULN) • Neutrophils > 1500 mm3 • Platelets > 100 000/µl • Hemoglobin > 10g/dl • Serum creatinine < 1.5 x ULN or glomerular filtration rate (GFR) of ≥ 60 ml/minute. The GFR is to be based upon the Cockroft-Gault formula for creatinine clearance: GFR (ml/min) = c x (140 – age [years]) x weight (kg) 72 x serum creatinine (mg/100 ml) where c = 0.85 for female subjects and c = 1.00 for male subjects 11. If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing. [Females of childbearing potential are defined as any females who have experienced menarche and have not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy), or are not post menopausal (defined as age-related amenorrhea for ≥12 consecutive months)]
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E.4 | Principal exclusion criteria |
1. Previous chemotherapy 2. Radiotherapy or major surgery within the last 4 weeks prior to the start of study treatment 3. Prior treatment with an EGFR signal transduction directed therapy 4. Uncontrolled angina pectoris, heart failure, clinically significant uncontrolled cardiac arrhythmias 5. Clinically significantly abnormal electrocardiogram (ECG) or cardiac history (e.g. subjects with myocardial infarction within the last 6 months) 6. Treatment with non-permitted medication (as specified in Section 6.8). 7. Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease. 8. Superior vena cava syndrome contra-indicating hydration 9. Symptomatic peripheral neuropathy NCI-CTCAE grade ≥2 and/or ototoxicity grade ≥2, except if due to trauma or mechanical impairment due to tumor mass 10. Known active, uncontrolled infections, uncontrolled severe organ dysfunction or metabolic disorder or any other significant disease which in the investigator’s opinion would exclude the subject from the study 11. Pregnancy (confirmed by β-HCG) or lactation period 12. Known hypersensitivity to matuzumab or any of the components of ECX (according to the current investigators’ brochure for matuzumab and the relevant product information sheets for epirubicin, cisplatin and capecitabine) 13. Known conditions that would interfere with treatment with any of the substances used in this study 14. Participation in another clinical study within the past 30 days 15. Concurrent malignancies or invasive cancers diagnosed within the past 5 years, except for: adequately treated basal cell cancer of the skin or in situ cancer of the cervix 16. Legal incapacity or limited legal capacity
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary target variable is the tumor response rate based on response assessments made by the Independent Review Committee. Subjects in both groups will be evaluated for tumor response every 6 weeks during treatment (regardless of any treatment delays), and every 3 months after the end of all study treatment, until PD. Response will be classified according to the modified WHO criteria. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
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 | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Analysis of the data from this study (study end) will be carried out 6 months after the last patient has had their end of study visit to allow collection of data on survival. The overall study duration for a total of 70 subjects is anticipated to be about 21 months i.e. from 3rd quarter 2005 to 1st quarter 2007. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |