A randomised, double blind, placebo-controlled, multi-centre study to evaluate the efficacy and safety of bevacizumab in combination with docetaxel compared with docetaxel plus placebo, as first line treatment for patients with HER2 negative metastatic and locally recurrent breast cancer - AVADO
- Conditions
- Metastatic breast cancerMedDRA version: 8Level: PTClassification code 10055113
- Registration Number
- EUCTR2005-003862-40-SE
- Lead Sponsor
- F. Hoffmann-La Roche Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 705
1.Female only.
2.Age >= 18 years.
3.Able to comply with the protocol.
4.ECOG PS of 0 or 1
5.Life expectancy of >= 12 weeks.
6.Written informed consent (Informed Consent document to be approved by the institution’s Independent Ethics committee [IEC]) obtained prior to any study specific screening.
7.Patients with histologically or cytologically confirmed, HER 2 negative, pre- or postmenopausal adenocarcinoma of the breast with measurable or non measurable locally recurrent or metastatic disease, who are candidates for chemotherapy. Locally recurrent disease must not be amenable to resection with curative intent.
8.Documented ER/PR status.
9.Prior adjuvant/neo-adjuvant chemotherapy is allowed as long as the last dose of chemotherapy was not within 6 months prior to randomization. However, if chemotherapy:
-was taxane based, patients are only eligible if they received their last chemotherapy =12 months prior to randomization.
-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.
10.Adequate left ventricular ejection function at baseline, defined as LVEF not below the institutional lower limit of normal by either echocardiogram or MUGA.
11.The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR, or appropriate monitoring test is within therapeutic limits and the patient has been on a stable level of anticoagulation for at least two weeks at the time of randomization:
-Patients on heparin treatment should have an aPTT between 1.5-2.5 x ULN (or patient value before starting heparin treatment).
-Patients on low molecular weight heparins should receive daily dose of 1.5–2.0 mg/kg (of enoxaparin) or appropriate dose of the correspondent anticoagulant, according to package insert.
-Patients on coumarin derivatives should have an INR between 2.0 and 3.0 assessed at baseline in two consecutive measurements 1–4 days apart.
Patients not receiving anti coagulant medication must have an INR <= 1.5 and aPTT <= 1.5 x ULN within 7 days prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Previous chemotherapy for metastatic or locally recurrent breast cancer.
–Prior hormonal therapy for locally recurrent or metastatic disease is allowed but must have been discontinued at least 2 weeks prior randomization.
2.Patients must have received no radiotherapy for the treatment of metastatic or locally recurent/advanced disease, however patients who have received adjuvant/neo-adjuvant radiotherapy as part of the treatment of early breast cancer are eligible if the last fraction of radiotherapy was administered occurred at least 6 months prior to randomization. Radiotherapy administered for the relief of metastatic bone pain is allowed prior to study entry, but
–No more than 30% of marrow-bearing bone should have been irradiated
–The last fraction of radiotherapy should not have been administered within 3 weeks prior to randomization.
3.Other primary tumors within the last 5 years before randomization, except for adequately controlled limited basal cell, or squamous carcinoma of the skin, or carcinoma in situ of the cervix
4.Evidence of spinal cord compression or brain metastases. A CT or MRI of the brain must be performed within 4 weeks prior to randomization if the presence of metastases at these sites is suspected.
5.History or evidence upon physical/neurological examination of CNS disease unrelated to cancer, unless adequately treated with standard medical therapy e.g. uncontrolled seizures.
6.Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study treatment.
7.Minor surgical procedures, within 24 hours prior to randomization.
8.Pre-existing peripheral neuropathy > CTC grade 2 at randomization
9.Inadequate bone marrow function: ANC: < 1.5 x 109/L, Platelet count < 100 x 109/L and Hemoglobin < 9 g/dL.
10.Inadequate liver function:
-Serum (total) bilirubin above the normal limit for the institution
-AST & ALT >2.5 x ULN
Patients are not eligible for the study if they have:
–AST or ALT levels greater than 1.5 times ULN concurrent with serum alkaline phosphatase levels of greater than 2.5 times the ULN at baseline
11.Inadequate renal function
–Serum Creatinine >2.0 mg/dL or 177 micro mol/L
–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/24hr.
12.Chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (>75 mg/day).
13.Chronic daily treatment with corticosteroids (dose of >= 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
14. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
15.Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: CVA/stroke (= 6 months prior to randomization), myocardial infarction (= 6 months prior to randomization), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
16. Serious non-healing wound, peptic ulcer, or bone fracture.
17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of randomization.
18. Active infection requiring i.v. antibiotics at randomization
19. Pregnant or lactating females.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method