E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically or cytologically verified upper gastro-intestinal carcinoma, including carcinomas of the esophagus, cardia, stomac, pancreas, gall bladder, and bile ducts of the following histological subtypes: adenocarcinoma, planocellular or squamous cell carcinoma, and anaplastic/high-grade or undifferentiated carcinoma |
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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 |
To determine the median time to progression (TTP) and response rate (RR) of the combination of erlotinib and bevacizumab in patients with advanced upper gastro-intestinal carcinomas, refractory or intolerant to standard systemic therapy. |
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E.2.2 | Secondary objectives of the trial |
To determine safety, tolerability and toxicity. To determine median and overall survival (OS). To correlate efficacy of treatment with the expression of tumor markers obtained in serum (EFGR, bFGF, p-VEGF-A, and sVEGF-R2), in paraffin embedded tumor tissue (micro vessel density (MVD), and expression of VEGFR and EGFR, after immunostaining), and in fresh frozen tumor biopsies (micro array-based analyses of patterns of gene expression).
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Histologically or cytologically verified upper gastro-intestinal carcinoma, including carcinomas of the esophagus, cardia, stomac, pancreas, gall bladder, and bile ducts of the following histological subtypes: adenocarcinoma, planocellular or squamous cell carcinoma, and anaplastic/high-grade or undifferentiated carcinoma. PS 0-2 (ECOG scale) Age over 18 years Life expectancy > 3 months Sufficient organ function, defined as: Platelets > 100 x 109/liter Leukocytes > 3,0 x 109/liter ACN > 1,5 x 109/liter ASAT and/or ALAT < 3 x upper normal limit Bilirubin < 1,5 x upper normal limit EDTA clearance > 45 ml/min APTT and INR < normal limit Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. Fertile males must use preservatives.
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E.4 | Principal exclusion criteria |
Radiotherapy or chemotherapy within the last 4 weeks Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids Any prior EGFR- or VEGFR-based therapy Any condition (medical, social, psychological), which would prevent adequate information and follow-up Tumor located close to major blood vessels and judged to possess a high risk of serious bleeding Any other active malignancy, except basal or squamous cell carcinoma of the skin, or carcinoma in situ Any significant cardiac disease (New York Heart Association Class II or greater), significant arrythmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris Clinically significant peripheral vascular disease Evidence of coagulapathy Use of ASA, NSAIDs or clopidogrel Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment, anticipation of need for major surgical procedure during the curse of the study Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to treatment History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to treatment Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound or ulcer Pregnancy or breast feeding Ongoing therapeutic anti-coagulation Hypertension with blood pressure > 150/100 mmHg
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E.5 End points |
E.5.1 | Primary end point(s) |
median time to progression (TTP) and response rate (RR) safety, tolerability and toxicity. median and overall survival (OS).
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |