E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic cancer of the colon or rectum |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
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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 confirm the efficacy of bevacizumab in combination with oxaliplatin and capecitabine (XELOX) based regimen, based on progression free survival |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety profile of bevacizumab in combination with oxaliplatin and capecitabine (XELOX) based regimen. - To determine the overall response rate, time to response, duration of response, overall survival rate, percentage of R0 resectability of metastatic lesions and quality of life of patients treated with bevacizumab in combination with oxaliplatin and capecitabine (XELOX) |
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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 proven diagnosis of colorectal cancer - Locally advanced or metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease - Age ≥ 18 - ECOG Performance Status 0-1 (Appendix III) - Life expectancy of at least 12 weeks - At least one measurable lesion according to RECIST criteria - Neutrophils ≥1.5 x 109/L and Platelets ≥100 x 109/L - Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤2.5 x UNL, or ≤5 x UNL in case of liver metastases, alkaline phosphatase ≤2.5 x UNL, ≤5 x UNL in case of liver metastases. - Creatinine clearance >50 mL/min or serum creatinine ≤1.5 x UNL - Urine dipstick of proteinuria <2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein/24 hr. - Written informed consent. - Patients must be accessible for treatment and follow up. - Patients registered on this trial must be treated and followed at the participating Center. |
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E.4 | Principal exclusion criteria |
- Radiotherapy to any site within 4 weeks before the study. - Untreated brain metastases or spinal cord compression or primary brain tumours. - History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke). - Serious, non-healing wound, ulcer, or bone fracture. - Evidence of bleeding diathesis or coagulopathy. - Uncontrolled hypertension. - Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. - Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. - Chronic, daily treatment with high-dose aspirin (>325 mg/day). - Treatment with any investigational drug within 30 days prior to enrolment. - Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications. - Other co-existing malignancies or malignancies diagnosed within the last 5 years. - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. - Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication. - Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of nonchildbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. - Symptomatic peripheral neuropathy ≥grade 1 according the NCI Common Toxicity Criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS), defined as the time period from the start of study medication to disease progression or death from any cause. |
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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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |