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 | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
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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 if the efficacy of bevacizumab in combination with capecitabine is superior to capecitabine monotherapy, 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 as compared with capecitabine monotherapy
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E.2.3 | Trial contains a sub-study | No |
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 >= 70 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 histological/cytological confirmation of diagnosis is required in case the time interval from last histological/cytological diagnosis to starting study treatment exceeds 3 years) 5) Diagnosis of metastatic disease not more than 6 months prior to starting study treatment. Patient with relapsed metastatic disease after a R0 resection of liver metastases will also be eligible providing that the relapse was diagnosed not more than 6 months prior to starting study treatment. 6) At least one measurable metastatic lesion, measurable or at least evaluable disease (as per RECIST criteria) 7) Prior adjuvant (or neo-adjuvant for rectal cancer patients) chemotherapy allowed if completed more than 6 months before starting study treatment. 8) ECOG performance score of 0 – 2 (see Appendix 4) 9) Life Expectancy of at least 3 months 10) Adequate haematological function: ANC >= 1.5 x 10Exp9/L; platelets >= 100 x 10Exp9/L, Hb >= 9 g/dL within 7 days prior to starting study treatment 11) INR <= 1.5; PTT <= 1.5 × ULN within 7 days prior to starting study treatment 12) Adequate liver function: Serum bilirubin <= 1.5 x ULN; AST / ALP <= 2.5 x ULN (in case of liver metastases < 5 × ULN) within 7 days prior to starting study treatment 13) Calculated creatinine clearance >= 30 mL/min (measured using the Cockroft and Gault formula, see Appendix 7) within 7 days prior to starting study treatment. 14) Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24-hour urine must demonstrate <= 1 g of protein in 24 hours within 7 days prior to starting study treatment. 15) Patients with metastatic colorectal cancer, not candidates for curative resection of metastatic lesions and not optimal candidates for a combination chemotherapy including irinotecan or oxaliplatin
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E.4 | Principal exclusion criteria |
1) Patients who received adjuvant antiVEGF treatment 2) Prior chemotherapeutic treatment for metastatic CRC 3) Clinical evidence of brain metastases or 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) or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake 4) Past or current history (within the last 5 years prior to starting study treatment) 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 starting study treatment), myocardial infarction (<= 6 months before starting study treatment), unstable angina, NYHA >= grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension 6) Patients must not have received treatment with any other investigational agent within 30 days prior to starting study treatment. 7) Known hypersensitivity to any of the study drugs 8) Current or recent (within 10 days of first dose of study treatment) daily use of aspirin (> 325 mg/day) or other NSAID 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. Patients receiving (or considered candidate to receive) anticoagulants agents as prophylaxis of cardiovascular risk, should continue (or start) the appropriate treatment at study entry 10) History of thromboembolic or haemorrhagic events within 6 months prior to starting study treatment 11) History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 month prior to starting study treatment 12) Evidence of clinical significant bleeding diathesis or coagulopathy 13) Serious, non healing wound, ulcer, or bone fracture 14) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to starting study treatment 15) 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 (e.g. serious intercurrent infections, other serious uncontrolled concomitant disease) 16) Patients who don’t have an intact GI (e.g. clinically significant malabsorption syndrome) and those who are unable to take oral medication (e.g. swallowing difficulty) 17) Male patients, with partners of childbearing potential who are not willing to use effective means of contraception whilst on treatment and for 90 days after last dose of the study drug. 18) Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine 19) Organ allografts requiring immunosuppressive therapy
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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 date of randomisation until disease progression or death from any cause, whichever occurs first. Patients without an event will be censored at the date of last assessment, last documented tumour assessment, or in case none of these are available, at the date of randomisation. Disease progression will be based on the investigator’s assessment; evaluation of target lesions and non target lesions will be in accordance with the RECIST criteria. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | Yes |
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 is defined as the date of the final scheduled clinic visit of the last patient to complete the study or the date on which the last data point from the last patient has been received, whichever is the later. |
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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 | 9 |
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 | 9 |