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, HER2 negative breast carcinomaMedDRA version: 14.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2005-003862-40-IT
- Lead Sponsor
- F. Hoffmann - La Roche Ltd
- 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 chemotherapy is allowed as long as the last dose of chemotherapy was not within 6 months prior to randomization. However, if adjuvant chemotherapy: was taxane based, patients are only eligible if they received their last adjuvant 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 dose of anticoagulants for at least two weeks at the time of randomization. Patients not receiving anti coagulant medication must have an INR < 1.5 and aPTT < 1.5 x ULN within 7 days of randomization.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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
Exclusion Criteria 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 3 weeks prior randomization. 2.Patients must have received no radiotherapy for the treatment of metastatic disease, however patients who have received 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, and or AST & ALT >2.5 x ULN ( > 5 x ULN in patients with liver metastases) Patients are not eligible for the study if they have: AST/ALT levels greater than 1.5 times ULN concurrent with serum alkaline phosphatase levels of greater than 2.5 times the ULN at baseline or ALT/AST greater than ULN concurrent with alkaline phosphatase greater than 6 times the upper limit of normal 11.Inadequate renal function Serum Creatinine >2.0 mg/dL or 177 micromol/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 or 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-ab
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