E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Tratamiento de pacientes con cáncer de mama metastático negativo para HER-2 que no han manifestado progresión durante el tratamiento de primera línea con docetaxel más bevacizumab. 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 | 9.1 |
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 patient?s 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 Maintenance treatment phase: 1. Patients must have SD, PR or CR per RECIST by the end of the initial treatment phase with bevacizumab plus docetaxel. Those patients who meet the response criteria at cycle 6 can be immediately randomised into the maintenance treatment phase (without needing to wait for results a confirmatory scan). Note: in the event that a patient is found to be responding at cycle 3 but is experiencing toxicities that would require a dose-interruption, investigators can use their discretion to immediately randomise the patient to the maintenance treatment phase. |
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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. 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). 17. Major surgical procedure within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment. 18. Minor surgical procedures, within 24 hours prior to the first study treatment. 19. History of uncontrolled seizures, CNS disorders or psychiatric disability judged by the Investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake. 20. Pre-existing peripheral neuropathy >CTC grade 2. 21. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. 22. Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke within ?6 months prior to the first study treatment, myocardial infarction within ?6 months prior to the first study treatment, unstable angina, NYHA grade II or greater CHF, or serious cardiac arrhythmia requiring medication. 23. History of abdominal fistula, grade 4 bowel obstruction or gastrointestinal perforation, intra-abdominal abscess within 6 months prior to randomisation. 24. Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medications. 25. Serious non-healing wound, peptic ulcer or bone fracture. 26. Serious active infection requiring i.v. antibiotics at enrolment. 27. Prior unanticipated severe reaction to fluoropyrimidine therapy. 28. Known dihydropyrimidine dehydrogenase deficiency. 29. Known hypersensitivity to any of the study treatments or excipients. 30. Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanised antibodies. 31. Evidence of any other medical conditions that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is PFS, defined as the time from first study drug dosing (during the maintenance treatment phase) to the first documented disease progression or death, whichever occurs first. Progression will be based on tumour assessment made by the investigators according to the RECIST criteria. In this trial, PFS will be used to evaluate whether maintenance therapy with bevacizumab plus capecitabine compared to bevacizumab alone, further improves the response to treatment following initial therapy with bevacizumab plus docetaxel. |
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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 |
Tolerability; Markers of predictive value: ER/PgR; HER-2; Quality of life |
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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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
bevacizumab en monoterapia |
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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 | 8 |
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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Patient will be followed-up every 3 months after PD is documented. Each patient will be followed for 12 months for PFS and at least 24 months after the last patient have been enrolled. |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |