E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
locally advanced rectal carcinoma (cT3NxM0) |
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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 |
feasibility and tolerance of preoperative therapy with Bevacizumab in combination with Capecitabine and radiotherapy for patients with locally advanced, locally operable rectal carcinoma |
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E.2.2 | Secondary objectives of the trial |
collection of response rate (T- and M-downstaging, pathological complete remission) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title of sub-protocol: Measurement of the tumor vessel density with 3-Tesla-magnetic reesonance imaging before, durng and after neoadjuvant RadioChemo-Molucular Target Therapy (RC-NTTx) of the locally advanced rectum carcinoma within ABCSG study R04/TAKO 08
Version/Date of sub-protocol: Version 1.0, 04.12.2007
Primary objective: prediction of the response to the RadioChemotherapy by the use of quantitive measurement of tumor vessel density and tumor oxygenation |
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E.3 | Principal inclusion criteria |
- age: 18 – 80 - bioptical confirmed adenocarcinoma of the rektum in T3NxM0 status. The tumor has to be basically surgically complete resectable (->R0). - no former chemotherapy, no radiotherapy of pelvis or abdomen and/or tumor resection of rectum carcinoma - WHO performance status 0-2 - adequatic bone marrow reserve (granulocytes > 3.000/µl, absolute rate of neutrophile > 1,5x109/l, thrombocytes: > 100.000/µl, haemoglobin > 10 g/l) - adequate hepatic function (Bilirubin: < 1.5 x ULN, GOT und GPT < 2.5 x ULN) - adequate renal function (creatinin: < 1.25 mg/dl, Kreatinin-Clearance: > 50 ml/min (Cockroft and Gault Formel), proteinuria: dipstick < 2+. In case of dipstick > 2+ protein has to be meassured in 24h urine and does not exceed more than 1g /24h) - ability of intake of pills - women of childbearing potential: exclusion of pregnancy (negative urin or serum pregnancy test) - willigness of women of childbearing potential and accordingly of potent men to use approved contraceptives (e.g. birth-control pill, loop, condom) during and at least 3 month after conclusion of the study - life expectancy of at least 3 month - INR and aPTT < 1.5 ULN - signed Informed Consent before recruitment
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E.4 | Principal exclusion criteria |
- former radiothrapy of pelvis or abdomen - former chemotherapy - any other kind of malign tumor in the last 5 years - any other kind of tumour in the last 5 years with exceptence of basal cell carcinoma of skin and cervixcarcinoma in situ - general contraindiction or known hypersensitivity against Bevacizumab and/or Capecitabine - non malign disease, if there is a contraindiction with radiotherapy, or chemotherapy with Bevacizumab and Capecitabine, or a resection of rectum: uncontrolled hypertension (systolic > 150 mmHG and/or diastolic >100 mmHG) or clinical significant (e.g. active) cardiovascular disease: CVA (kardiovascular accident)/ cerbral apoplexia (< 6 moths before recruitment), myocardial infarct (< 6 months before recruitment), instabil angina pectoris, CHF with NYHA status II or higher, or treated serious arrhythmia, hepatic disease, significant neurologic or psychiatric disorders - florid, serious infections at the time of recruitment - legally limited contractual capability or evidence of neurological or psychiatric disease, if it will constrict the patients compliance in the opinion of the investigator - evidence of lacking cooperation of the patient - major intervention within 28 days before recruitment, open wounds - serious injuries, unhealed wounds or fractures - patients with spinal compressons or metastases in central nervous system - evidence of bleeding diathesis or coagulation dysfunction - actual intake of anticoagulant or thrombolytic agents, Aspirin > 325 mg/d or within 10 days before study start) - actual or recent (within 10 days before recruitment) therapeutic therapy with fully-dosed anticoagulants. A prophylactic treatment is permitted. - previous thromboembolic or hemorraghic events within the last 6 months before recruitment - previous abdominal fistulas, GI perfoation or intra-abdominal abscess within the last 6 months - treatment with other study medication within 28 days before recruitment - patients with malabsorption syndrome or difficulties swallowing - pregnant or breast feeding women - proteinuria: dipstick <2+. If the dipstick protein is > +2 protein has to be measured in the urine of 24h. The maximum value of protein can be 1g/24h |
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E.5 End points |
E.5.1 | Primary end point(s) |
feasibility and tolerance of preoperative therapy with bevacizumab (Avastin) in combination with capecitabine (Xeloda) and radiotherapy for patients with locally advanced rectal carcinoma |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
feasibility and tolerance of therapy |
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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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 21 |