E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic cancer of the colon or rectum. |
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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 assess the safety profile of bevacizumab when combined with fluoropyrimidine-based chemotherapy regimens as first line treatment of metastatic cancer of the colon or rectum.
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E.2.2 | Secondary objectives of the trial |
To assess the effectiveness of bevacizumab as measured by time to disease progression and duration of survival. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Patients with histologically confirmed diagnosis of metastatic CRC, untreated yet with chemotherapy for metastatic disease (prior adjuvant chemotherapy for colorectal cancer allowed), who are scheduled to start first line fluoropyrimidine-based chemotherapeutic treatment. 2. Age ≥ 18. 3. Measurable or non-measurable disease. 4. Performance status ECOG performance status 0 or 1. 5. Life expectancy greater than 3 months. 6. Neutrophils ≥ 1’500/µl, Platelets ≥ 100’000/µl, AST/ALT ≤ 2.5 × ULN (< 5 × ULN if liver metastases), Alkaline phosphatase ≤ 2.5 × ULN, Serum bilirubin ≤ 1.5 × ULN, Serum Creatinine ≤ 1.5 × ULN. Urine dipstick of proteinuria <2+. Patients discovered to have equal to or greater than 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate equal to or less than 1 g of protein/24 hr. 7. Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the study drug. She and her partner should prevent pregnancy (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) up to at least 6 months after last treatment completion or the last drug dose, whatever happens first. 8. Signed written informed consent according to ICH/GCP and the local regulations (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) will be obtained prior to any study specific screening procedures. 9. Patient must be able to comply with the protocol |
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E.4 | Principal exclusion criteria |
1. Treatment with first-line chemotherapy for metastatic CRC. 2. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 (Patients must have recovered from any major surgery), or anticipation of need for major surgical procedure during the course of the study. 3. Planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed). 4. Clinical or radiological evidence of CNS metastases. 5. Past or current history (within the last 5 years) of malignancies except for the indication under this study and curatively treated: - Basal and squamous cell carcinoma of the skin - In-situ carcinoma of the cervix 6. Serious non-healing wound or ulcer. 7. Evidence of bleeding diathesis or coagulopathy. 8. Uncontrolled hypertension. 9. 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. 10. Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes i.e. except for anticoagulation for maintenance of patency of permanent indwelling IV catheters. 11. Treatment with any investigational drug (including IMMP, EGFR inhibitors, COX-2 inhibitors) or participation in another investigational study within 30 days prior to enrolment. 12. Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications 13. Ongoing treatment with aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration 14. Pregnancy (positive serum pregnancy test) and lactation 15. Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
The intent to treat (ITT) population, which includes all patients receiving at least one dose of study drug, will be used for reporting the safety information. All safety parameters will be analysed and presented in terms of listings and summary tables. Adverse events and laboratory parameters will be assessed according to the National Cancer Institute Common Toxicity Criteria grading system (NCI CTC) (version 3.0, 2003). Adverse events will be displayed in standard frequency tables. For laboratory parameters, descriptive summary tables of change from baseline over time based on SI units will be produced. Shift tables of changes in NCI CTC grades will also be provided for laboratory parameters, with worst changes displayed. Descriptive summary tables of change from baseline over time will be provided for vital signs parameters. |
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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 | 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) | 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 | 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.8.5 | 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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The end of the trial will be the date of the last visit of the last patient (30 days after last study medication). However patients will be followed up for specific adverse events following the closure of 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 | |
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 |