E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
FIRST LINE METASTATIC COLORECTAL CARCINOMA |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
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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 |
To determine the efficacy of bevacizumab in combination with capectabine, based on progression free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety profile of bevacizumab in combination with capecitabine To determine the overall response rate (RR), time to response, duration of response and overall survival (OS) of bevacizumab in combination with capecitabine |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Written informed consent Age >= 70 years Histologically or cytologically confirmed carcinoma of the colon and/or rectum Diagnosis of metastatic disease not more than 6 months prior to enrolment At least one measurable metastatic lesion (as per RECIST criteria) Prior adjuvant (or neo-adjuvant for rectal cancer patients) chemotherapy allowed if completed more than 6 months before inclusion ECOG performance score of 0 – 2 Live expectancy > 3 month Absolute neutrophil count (ANC) >= 1.5 × 109/L Platelet count >= 100 x 109/L Hemoglobin >= 9 g/dL (may be transfused to maintain or exceed this level) International Normalised Ratio (INR) <= 1.5 International normalized ration (INR) <= 1.5 and partial thromboplastin time (PPT) <= 1.5 x upper limit of normal (ULN) Total bilirubin <= 1.5 x ULN AST and ALP <= 2.5 times ULN, 5x ULN in patients with liver metastases Calculated creatinine clearance >=50 mL/min Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24- hour urine must demonstrate <= 1 g of protein in 24 hours |
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E.4 | Principal exclusion criteria |
Patients who received adjuvant anti-VEGF treatment Prior chemotherapeutic treatment for metastatic CRC Clinical evidence of brain metastases or history or evidence upon physical examination of CNS disease unless adequately treated Past or current history (within the last 5 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible) Clinically significant cardiovascular disease, for example CVA (<= 6 months before treatment start), myocardial infarction (<= 6 months before treatment start), unstable angina, NYHA >= grade 2, CHF, arrhythmia requiring medication, or uncontrolled hypertension Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study Known hypersensitivity to any of the study drugs Current or recent (within 10 days of first dose of study treatment) daily use of aspirin (> 325 mg/day) or other NSAID Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes. Patients receiving (or considered candidate to receive) anticoagulants agents as prophylaxis of cardiovascular risk, should continue (or start) the appropriate treatment at study entry History of thromboembolic or haemorrhagic events within 6 months prior to treatment History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 month prior to enrolment Evidence of bleeding diathesis or coagulopathy Serious, non healing wound, ulcer, or bone fracture Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications Patients who don't have an intact GI tract and those who are unable to take oral medications Men of childbearing potential not willing to use effective means of contraception Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine Organ allografts requiring immunosuppressive therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS, defined as the time period from thedate of randomisation until disease progression or death, whichever occurs first. |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
COMBINAZIONE VERSO ALTRO FARMACO |
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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
| |
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 | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |