E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated metastatic colorectal cancer |
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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 |
Phase II stage Primary Objective: • To determine the relative toxicity of the combination of capecitabine and bevacizumab and the combination of capecitabine, mitomycin C (MMC) and bevacizumab with that of capecitabine monotherapy.
Phase III stage Primary Objective: • To compare progression-free survival (PFS) on the three arms |
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E.2.2 | Secondary objectives of the trial |
Phase II stage Secondary Objective: • To assess tumour response rate (RECIST criteria) for each arm
Phase III stage Secondary Objectives: • To determine treatment related toxicity. • To determine tumour response rates ( RECIST criteria) • To determine overall survival for each treatment arm. • To compare disease related symptoms and Quality of life. • To determine cost effectiveness of bevacizumab containing treatments. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a) Histological diagnosis of colorectal cancer b) Metastatic disease that is not resectable c) Age > 18 years d) Any patient in whom the investigator considers capecitabine monotherapy appropriate e) Measurable and/or non-measurable disease as assessed by CT scan f) ECOG performance status 0, 1 or 2. Patients with PS2 should have serum albumin >30 g/L g) No prior chemotherapy except for adjuvant chemotherapy given in association with (i) complete resection of primary colon or rectal cancer provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment and/or (ii) complete resection of limited colorectal metastases to liver and/or lung provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment h) Adequate bone marrow function with platelets > 100 X 109/l; neutrophils > 1.5 X 109/l i) Adequate renal function, with calculated creatinine clearance >30 ml/min (Cockcroft and Gault). For patients with creatinine clearance <50 ml/min the starting dose of capecitabine may not be greater than 2000 mg/m2/d (see Section 7.1) j) Adequate hepatic function with serum total bilirubin < 1.5 X upper limit of normal range k) Life expectancy of at least 12 weeks l) No other concurrent uncontrolled medical conditions m) No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse n) Women and partners of women of childbearing potential must agree to use adequate contraception o) Written informed consent |
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E.4 | Principal exclusion criteria |
a) Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or to complete the protocol b) Patients with a lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes. c) Uncontrolled hypertension d) Active bleeding disorders within the last 3 months e) Patients on full anticoagulation with warfarin. (Patients who require full anticoagulation and who wish to participate in the study should be converted to low molecular weight heparin). (Note: patients receiving full anticoagulation with low molecular weight heparin should have no evidence of tumour invading or abutting major blood vessels on any prior CT scan) f) Participation in any investigational drug study within the previous 8 weeks g) Patients with uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris h) Patients with a history of acute myocardial infarction or cerebrovascular accident within the last 12 months i) Regular use of aspirin (>325mg/day) or NSAIDs (low dose aspirin (<325 mg/d), or occasional use of NSAIDs is acceptable) j) CNS metastases k) Major surgical procedure within the last 28 days l) Serious non-healing wound, ulcer or bone fracture m) 24 hour urinary protein > 2g/ 24 hours ( performed if urine dipstick > 1+ ) n) Pregnancy or lactation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase II stage Primary Endpoint: Treatment-related toxicity
Phase III stage Primary endpoint: Progression free survival (PFS) |
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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 | 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) | Yes |
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 | 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) | Yes |
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 | No |
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
|
The end of the study is defined as such time as the last patient has had their last visit. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |