Open-label study of bevacizumab Avastin plus taxane monotherapy or in combination for the first-line treatment of patients with locally recurrent or metastatic breast cancer. - ATHENA

• Conditions: ocally, recurrent LR or metastatic breast cancer mBC , HER-2 negative patients who have not received prior chemotharapy for LR or mBC. HER-2 positive patients are eligible if they have disease progression after previous trastuzumab Herceptin treatment in the adjuvant setting.; MedDRA version: 6.1Level: PTClassification code 10006198

• Registration Number: EUCTR2006-002529-21-IT
• Lead Sponsor: ROCHE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-24
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 2291

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 8805;18 years 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 LR or metastatic disease, who are candidates for chemotherapy. Locally recurrent disease must not be amenable to radiation therapy or resection with curative intent HER2-positive patients are eligible if they have progressed after previous trastuzumab Herceptin treatment in the adjuvant setting 5. Eastern Cooperative Oncology Group ECOG performance status PS 0-2 6. Life expectancy of 8805;12 weeks 7. Prior adjuvant chemotherapy is allowed8. 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 if using chemotherapy backbone which is highly myelosuppressive 9. Adequate haematological function Absolute neutrophil count ANC 8805;1.5 x 109/L AND Platelet count 8805;100 x 109/L AND Haemoglobin 8805;9 g/dL may be transfused to maintain or exceed this level 10. 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 11. Adequate renal function Serum creatinine 8804;1.25 x ULN or calculated creatinine clearance 8805;50 mL/min AND Urine dipstick for proteinuria 2 . Patients discovered to have 8805;2 proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate 8804;1 g of protein in 24 hours 12. International normalized ratio INR 8804;1.5 and PTT 8804;1.5 x ULN within 7 days prior to enrolment 13. 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. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test within 7 days prior to the first dose of bevacizumab is required
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

Exclusion Criteria

1. Previous chemotherapy for LR or mBC 2. Concomitant hormonal therapy for LR or metastaticdisease, however previous hormonal therapy is allowed for adjuvant, LR, or mBC 3. Patients must have received no radiation therapy forthe treatment of metastatic disease apart from those who received it for the relief of metastatic bone painand with the precautions mentioned above 4. Evidence of CNS metastases even if previously treated . If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases 5. Pre-existing peripheral neuropathy NCI CTC-AE Grade 2 at enrolment 6. Major surgery including open biopsy , significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment 7. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion 8. Current or recent within 10 days of first dose of bevacizumab use of aspirin 325 mg/day 9. Current or recent within 10 days of first dose of bevacizumab use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed 10. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding 11. Uncontrolled hypertension systolic 150 mmHg and/or diastolic 100 mmHg 12. Clinically significant i.e. active cardiovascular disease for example CVA 8804;6 months before enrolment , myocardial infarction 8804;6 months before enrolment , unstable angina, congestive heart failure CHF NYHA Class 8805;II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication 13. Non-healing wound, active peptic ulcer or bone fracture 14. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment 15. Women with an intact uterus unless amenorrhoeic for the last 24 months not using effective, nonhormonal means of contraception intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile during the study and for a period of 6 months following the last administrationof bevacizumab. 16. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of bevacizumab 17. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment 18. Known hypersensitivity to bevacizumab and any of its excipients, and any of the chemotherapies 19. Evidence of any other disease, neurological 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety profile of bevacizumab when combined with taxane monotherapy or in combination as first line treatment of patients with LR or mBC.;Secondary Objective: - To assess the efficacy of bevacizumab when combined with taxane monotherapy or in combination as first line treatment of patients with LR or mBC as measured by time to disease progression TTP and overall survival OS . - To assess the safety of bevacizumab in patients who develop CNS metastases during and for 6 months following the treatment period.;Primary end point(s): The incidence of SAEs related to bevacizumab and the incidence of specific AEs serious and non-serious such as hypertension, proteinuria, arterial and venous thromboembolism, CHF, CNS bleeding, other haemorrhages, wound-healing complications, and gastrointestinal perforations, are considered as primary end points. Patients with ECOG PS2 will be analyzed separately.