E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or locally recurrent HER2-negative breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006198 |
E.1.2 | Term | Breast cancer recurrent |
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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 |
Primary objective: • Time to disease progression (TTP)
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E.2.2 | Secondary objectives of the trial |
Secondary objectives • Objective response rate (ORR) in patients with measurable disease at baseline • Clinical benefit (CR + PR + SD) in patients with measurable disease at baseline • Progression-free survival (PFS) • Overall survival (OS) • Safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for the study, each patient must fulfil all of the following inclusion criteria: 1. Signed informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements; 2. Age ≥ 70 years; 3. Pathologically confirmed and documented metastatic breast cancer or locally recurrent breast cancer not amenable to curative treatment. Complete radiology and tumor measurement workup must be completed within 4 weeks prior to first study treatment; 4. Measurable disease according to RECIST criteria; 5. HER2 negative disease; 6. No prior treatment for metastatic or locally recurrent disease; 7. Prior radiotherapy is allowed if delivered at least 2 weeks before enrolment in the study and for the relief of metastatic bone pain, and provided that no more than 30% of marrow-bearing bone was irradiated and that target lesions were not included in the radiotherapy field; 8. Not suitable for aggressive chemotherapy regimen in the opinion of the investigator; 9. Performance status ECOG 0 – 2.
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E.4 | Principal exclusion criteria |
1. Any prior neoadjuvant or adjuvant treatment with anthracyclines completed less than 6 months prior to enrolment. The maximum cumulative dose received must not have exceeded 360 mg/m2 for doxorubicin or 720 mg/m2 for epirubicin. Prior anti-epidermal growth factor therapy is allowed; 2. Concurrent hormonal therapy; however previous hormonal therapy is allowed for adjuvant, locally recurrent, or metastatic breast cancer if completed within ≥1 months prior to enrollment; 3. History or clinical evidence of brain metastases. If there is any clinical suspicion of brain metastasis, a computerized tomography (CT) scan or magnetic resonance imaging (MRI) of the brain must be conducted within 4 weeks prior to enrolment; 4. Other malignancy (including primary brain tumors) within the last 5 years, which could affect the diagnosis or assessment of breast cancer, except for adequately treated carcinoma in situ of the cervix, squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer; 5. Life expectancy < 12 weeks; 6. Any of the following abnormal values: • Inadequate bone marrow function: hemoglobin (Hb) < 8.0 g/dL, absolute neutrophil count (ANC) < 1.5 x 109/L, or platelet count < 100 x 109/L;Inadequate liver function: AST/SGOT or ALT/SGPT > 2.5 x upper limit of normal (ULN) or > 5 x ULN in patients with liver metastases), serum alkaline phosphatase > 2.5 ULN or > 5 x ULN in patients with liver metastases, or > 10 x ULN in patients with bone metastases or total bilirubin > 2 x ULN; Moderate or severe renal impairment: creatinine clearance ≤ 50 mL/min (calculated according to the Cockroft and Gault formula; see Appendix 1), or serum creatinine > 1.5 x ULN; 7. Chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (> 75 mg / day); 8. Chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids); 9. Requirement for concurrent use of the antiviral agents sorivudine or brivudine; 10. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to enrolment, or anticipation of the need for major surgery during the course of the study treatment; 11. Minor surgical procedures, within 24 hours prior to enrolment; 12. Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study. 13. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease, including: • Cerebrovascular accident/stroke (≤ 6 months prior to enrolment), • Myocardial infarction (≤ 6 months prior to enrolment), • Unstable angina, • New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF) • Serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia); 14. History or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding; • If the patient is receiving oral or parenteral anticoagulants, the dose must be stable for at least 2 weeks prior to the first study treatment and the INR, or appropriate monitoring test must be within therapeutic limits: - Patients on heparin treatment should have an aPTT between 1.5-2.5 x ULN (or value before starting heparin treatment); - Patients on low molecular weight heparins should receive 1.5–2.0 mg/kg of enoxaparin (or appropriate dose of a corresponding anticoagulant) daily, according to the respective prescribing information; - Patients on coumarin derivatives should have an INR between 2.0 and 3.0 confirmed at two consecutive measurements 1–4 days apart during screening; • Patients not receiving anti coagulant medication must have an INR 1.5 and aPTT 1.5 x ULN within 7 days prior to the first study treatment. 15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of enrolment; 16. Clinically significant malabsorption syndrome, or inability to take oral medication; 17. Serious active infection requiring IV antibiotics at enrolment, HIV, HBV, HCV; 18. Pleural effusion, unless clinically controllable; 19. History or evidence upon physical examination of CNS disease unrelated to cancer (e.g. uncontrolled seizures) unless adequately treated with standard medical therapy; 20. ect. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Patients will be treated with capecitabine plus bevacizumab until disease progression, unacceptable toxicity, or patient request for discontinuation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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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End of study is defined as the date of the last visit of the last patient. Patients will be followed up to one year after the enrolment of the last patient. |
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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 | 1 |
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 | 1 |
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 |