E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic colorectal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009954 |
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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 irinotecan and infusional 5-fluorouracil plus folinic acid based regimens as compared with historical controls, 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 irinotecan and infusional 5-fluorouracil plus folinic acid based regimens.
- To determine the overall response rate, time to response, duration of response, and overall survival of bevacizumab in combination with irinotecan and infusional 5-fluorouracil plus folinic acid based regimens as compared with historical controls. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures. 2. Age ≥18 years 3. Patient must be able to comply with the protocol. 4. Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases (new confirmation of metastatic disease is required in case the time interval from last histological/cytological diagnosis to enrolment exceeds 3 years). 5. Diagnosis of metastatic disease for which treatment will have to be started not more than 3 months prior to enrolment. 6. Life Expectancy of at least 3 months. 7. At least one measurable metastatic lesion (as per RECIST criteria) 8. Prior adjuvant or neo-adjuvant chemotherapy/radiotherapy allowed if completed more than 6 months before inclusion. 9. ECOG performance score of 0 or 1 10. Adequate haematological function: ANC ≥1.5 x 10(9)/L; platelets ≥ 100 x 10(9)/L, Hb ≥9 g/dL 11. INR ≤ 1.5; aPTT ≤ 1.5 x ULN within 7 days prior to starting study treatment 12. Adequate liver function: Serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) 13. Serum Creatinine ≤ 1.5 x ULN 14. Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24- hour urine must demonstrate ≤ 1 g of protein in 24 hours. 15. Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause. This test has to be reconfirmed by a urine test, should the 7 days window be exceeded. Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).
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E.4 | Principal exclusion criteria |
1. Patients who received adjuvant irinotecan or antiVEGF treatment 2. Prior chemotherapeutic treatment for metastatic CRC 3. Clinical evidence of brain metastases 4. Past or current history (within the last 2 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). 5. 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. 6. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study. 7. Known hypersensitivity to any of the study drugs. 8. Current or recent (within 10 days of first dose of study treatment) chronical use of aspirin (> 325 mg/day) or other NSAID with anti-platelet activity. 9. 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. 10. History of thromboembolic or haemorrhagic events within 6 months prior to treatment. 11. Evidence of bleeding diathesis or coagulopathy. 12. Serious, non healing wound, ulcer, or bone fracture. 13. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study. CVAD for chemotherapy administration inserted within 2 days prior to study treatment start. 14. 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. 15. Pregnancy or lactation 16. Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS), defined as the time period form the start of study medication to disease progression or death from any cause, 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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | 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 | 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 primary analysis of efficacy and safety endpoints will be performed when the last patient has completed 6 cycles (i.e. 12 weeks) of chemotherapy. For progression-free survival and overall survival, a follow-up analysis will be performed 12 months after last patient started therapy. |
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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 | |
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 |