E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-negative metastatic breast cancer that has not progressed during first-line docetaxel plus bevacizumab therapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast 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 evaluate whether maintenance therapy with bevacizumab plus capecitabine, compared to bevacizumab alone, can further increase Progression-Free Survival (PFS) in patients showing objective response or stable disease following initial therapy with bevacizumab plus docetaxel. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following parameters: During the initial treatment phase: Overall Response Rate (ORR) Clinical Benefit Rate (CBR) Safety and tolerability During the Maintenance treatment phase: ORR CBR Quality of life Time-to-Progression (TTP) Overall Survival (OS) Safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Initial treatment phase: 1. Signed informed consent obtained prior to initiation of any study specific procedures or treatment as confirmation of the patients awareness and willingness to comply with the study requirements 2. Age ≥ 18 years 3. Patients with histologically confirmed and documented, HER2-negative metastatic adenocarcinoma of the breast, who are candidates for taxane-based chemotherapy 4. Documented ER/PgR status 5. ECOG PS of 0-1; 6. Life expectancy of ≥ 12 weeks |
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E.4 | Principal exclusion criteria |
1. Previous chemotherapy for mBC. Prior hormone therapy for metastatic disease is allowed. 2. Prior adjuvant/neoadjuvant chemotherapy within 6 m. prior to first study treatment administration. 3. Prior adjuvant/neoadjuvant anthracycline-based chemotherapy with a max. cumulative dose >360 mg/m2 for doxorubicin or >720 mg/m2 for epirubicin. 4. Prior radiotherapy for the treatment of metastatic disease. Radiotherapy administered for the relief of metastatic bone pain is allowed prior to study entry, as long as no more than 30% of marrow-bearing bone was irradiated. 5. Chronic daily treatment with aspirin (>325 mg/day) or clopidogrel (>75 mg/day). 6. Requirement for concurrent use of the antiviral agent sorivudine, or chemically related analogues, such as brivudine. 7. Chronic daily treatment with corticosteroids (dose of ≥10 mg/day methylprednisolone or equivalent), with the exception of inhaled steroids. 8. Current or recent treatment with another investigational drug or participation in another investigational study. 9. Inadequate bone marrow function: ANC: <1.5 x 10E9/l, platelet count <100 x 10E9/l or haemoglobin <8 g/dl. 10. Inadequate liver function, defined as: serum (total) bilirubin >1.5 x ULN for the institution AST/SGOT or ALT/SGPT >2.5 x ULN (>5 x ULN in patients with liver metastases) ALP >2.5 x ULN at baseline (>5 x ULN in patients with liver metastases, or >10 x ULN in patients with bone metastases). 11. Inadequate renal function, defined as: serum creatinine >1.5 x ULN creatinine clearance <50 ml/min (calculated according to Cockroft and Gault) urine dipstick for proteinuria >2+. Patients with ≥2+ proteinuria on dipstick analysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in the 24-hour urine. 12. Patients not receiving anticoagulant medication who have an INR >1.5 or an aPTT >1.5 x ULN within 7 days prior to first study treatment. Note: Patients receiving full dose oral or parenteral anticoagulants may be included in the study as long as anticoagulant dosing has been stable for at least two weeks prior to study entry and the appropriate coagulation monitoring tests are within local therapeutic limits. 13. Evidence of spinal cord compression or brain metastases. 14. Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. 15. Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. 16. Women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly). Et al. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this trial is to compare Progression Free Survival between both treatment arms after randomization defined as the time from first dose of the study drug during the maintenance therapy to the first documented disease progression or death, whichever occurs first. PFS will be analyzed using a stratified log rank test with the following stratification factors used for randomization: -ER+/ER- patients -Presence or absence of visceral metastasis -Stable disease / response / non-mesurable disease -LDH level < 1.5 x ULN / > 1.5 x ULN Results are presented descriptively as well as graphically using the Kaplan-Meier method. Median PFS estimates as well as associated 95% confidence intervals will be reported. |
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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 | 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 |
Tollerabilita`; marker predittivi: ER/PgR; HER-2; qualita` della vita |
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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 | 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 | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 | No |
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |