E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic breast cancer, HER 2 negative |
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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 | 10065348 |
E.1.2 | Term | Breast adenocarcinoma 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 the efficacy of the combination of biweekly docetaxel and bevacizumab in terms of progression free survival in patients previously untreated with chemotherapy for metastatic breast cancer |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy (overall response rate, overall survival, time to response, duration of response) and safety profiles. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Biomarker substudy Identification of biomarkers (from tumor and plasma) predictive for the level of benefit from bevacizumab treatment. |
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E.3 | Principal inclusion criteria |
1.Written informed consent (informed consent document to be approved by the Independent Ethics Committee [IEC]) obtained prior to any study-specific procedure 2.Age ≥18 years female 3.Able to comply with the protocol 4.Histologically or cytologically confirmed, HER2-negative, pre- or post-menopausal women with adenocarcinoma of the breast with measurable or non-measurable (bone only disease) metastatic disease, who are candidates for chemotherapy. 5.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 6.Life expectancy of ≥12 weeks 7.Prior neo-/adjuvant chemotherapy is allowed. However, if chemotherapy: was anthracycline based, the maximum cumulative dose of prior anthracycline therapy must not exceed 360 mg/m2 for doxorubicin and 720 mg/m2 for epirubicin. 8.Prior adjuvant taxane therapy is allowed, if disease free interval ≥ 6 months after completion of adjuvant therapy 9.Previous hormonal therapy is allowed for adjuvant or mBC 10.Prior radiation therapy is allowed if: -delivered in the adjuvant setting as a part of the treatment of early breast cancer -delivered prior to study entry for the relief of metastatic bone pain provided that no more than 30% of marrow-bearing bone has been irradiated. 11.Adequate haematological function -Absolute neutrophil count (ANC) ≥1.5 x 109/L AND Platelet count ≥100 x 109/L AND Haemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level) 12.Adequate liver function -Total bilirubin <1.5 x upper limit of normal (ULN) AND AST, ALT <2.5 x ULN in patients without liver metastases; <5 x ULN in patients with liver metastases 13.Adequate renal function Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥50 mL/min AND Urine dipstick for proteinuria <2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours 14.International normalized ratio (INR) ≤1.5 and PTT ≤1.5 x ULN within 7 days prior to enrolment. Anticoagulation treatment not allowed. 15.If female, should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to inclusion into the study.
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E.4 | Principal exclusion criteria |
1.Previous chemotherapy for mBC 2.Patients must have received no radiation therapy for the treatment of metastatic disease (apart from those who received it for the relief of metastatic bone pain and with the precautions mentioned above) 3.Evidence of CNS metastases (even if previously treated). If symptomatic, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases 4.Pre-existing peripheral neuropathy NCI CTC-AE Grade >2 at enrolment 5.Major surgery, significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment 6.Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion 7.Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (>325 mg/day) 8.Current or recent (within 10 days of first dose of bevacizumab) use of oral or parenteral anticoagulants or thrombolytic agents. 9.History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding 10.Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) 11.Clinically significant (i.e. active) cardiovascular disease for example CVA (≤6 months before enrolment), myocardial infarction (≤6 months before enrolment), unstable angina, congestive heart failure (CHF) NYHA Class ≥II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication 12.Non-healing wound, active peptic ulcer or bone fracture 13.History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment 14.Past or current history (within the last 5 years) of malignancies except for the indication under this study and curatively treated Basal and squamous cell carcinoma of the skin or In-situ carcinoma of the cervix 15.Treatment with any other investigational agent, or participation in another clinical drug trial within 28 days prior to enrolment 16.Evidence of any other disease, neurological, psychiatric or 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 17.History of trombotic disorders within last six months prior to enrolment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (defined as the time from baseline date to the time of investigator assessed disease progression according to RECIST criteria or death) |
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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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the trial is the date of the final scheduled visit for the last patient to complete the study. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |