A Randomized open label study of the effect of first line combination treatment with Avastin (bevacizumab) plus paclitaxel and gemcitabine Compared With Avastin (bevacizumab) plus paclitaxel on objective response rate in patients with Metastatic Breast Cancer - BEGETAX

• Conditions: Metastatic breast cancer, HER2-negative patients who have not received prior chemotherapy for mBC; MedDRA version: 9.1Level: LLTClassification code 10006285; MedDRA version: 9.1Level: LLTClassification code 10055113

• Registration Number: EUCTR2008-007057-12-IT
• Lead Sponsor: ROCHE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-03
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

Signed informed consent (informed consent document to be approved by the Independent Ethics Committee) obtained prior to initiation of any study-specific procedure or treatment as confirmation of the patient?s awareness and willingness to comply with the study requirements
Age ≥18 years
Able to comply with the protocol
Histologically or cytologically confirmed and documented metastatic breast cancer women, proven HER2-negativity (secondary lesion or primitive tumor), who are candidates for chemotherapy
Lesions not amenable to curative surgery or radiotherapy. Limited /single cutaneous lesions or limited bone metastatis are considered amenable to curative surgery or radiotherapy
Previous cytotoxic anthracycline-based adjuvant chemotherapy
Measurable/evaluable metastatic disease (RECIST criteria)
Karnofsky performance status ≥ 70
Life expectancy of ≥ 12 weeks
Adequate haematological function
Absolute neutrophil count ≥1.5 x 109/L AND
Platelet count ≥100 x 109/L AND
Hemoglobin ≥9 g/dL
Adequate liver function
Serum (total) bilirubin <1.5 x the upper limit of normal (ULN) AND
AST/SGOT or ALT/SGPT <2.5 x ULN in patients without liver metastases; <5 x ULN in patients with liver metastases
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 the 24-hours urine
Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) &#8804;1.5 and an activated Partial Thromboplastin Time (PTT) &#8804;1.5 x ULN within 7 days prior to enrolment
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

Previous endocrine therapy or chemotherapy for mBC (previous endocrine therapy in the adjuvant or neo-adjuvant setting is allowed) Concomitant hormonal therapy for metastatic disease Prior adjuvant/neo-adjuvant chemotherapy within 6 months prior to first study treatment administration. However, if chemotherapy: was taxane based, patients are only eligible if they received their last chemotherapy &#8805; 12 months prior to first study treatment. 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 Prior radiotherapy for the treatment of metastatic disease (radiotherapy administered for the relief of metastatic bone pain is allowed prior to study entry, provided that no more than 30 % of marrow-bearing bone has been irradiated; previous radiation therapy in the adjuvant or neo-adjuvant setting as a part of the treatment of early breast cancer is allowed) Evidence of CNS metastases (even if previously treated). If suspected, the patient should be scanned within 28 days prior to enrollment to rule out CNS metastases 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 or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer Pre-existing peripheral neuropathy NCI CTC-AE grade > 2 at enrolment Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrollment or anticipation of the need for major surgery during study treatment Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion Current (chronic daily) or recent (within 10 days of first dose of bevacizumab) treatment with aspirin (> 325 mg/day) or clopidogrel (>75 mg/day) 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) History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) Clinically significant (i.e. active) cardiovascular disease including cerebrovascular accident/stroke (&#8804;6 months before enrolment), myocardial infarction (&#8804;6 months before enrolment), unstable angina, congestive heart failure (CHF) NYHA Grade &#8805;II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication Non-healing wound, active peptic ulcer or bone fracture History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment Serious active infection requiring IV antibiotics at enrolment, HIV, HBV, HCV Women with an intact uterus (unless amenorrhoeic for the last 24 months or surgically sterile) not using effective means of contraception during the study and for a period of 6 months following the last administration of bevacizumab (etc.)

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy: objective response rate (CR and PR according to RECIST criteria);Secondary Objective: Efficacy: Progression-free survival (PFS), 1 year Overall survival (OS) Safety and tolerability: incidence of AEs Quality of Life;Primary end point(s): This phase II design implies a direct ?screening? comparison of the experimental therapeutic approach against a randomized standard-treatment control arm, within a trial with a moderate sample size<br>Rubinstein LV et al. suggested 20% for both &amp;#945; (1-sided) and &amp;#946; errors as appropriate for phase II screening trials<br><br>Therefore, assuming for the control arm a RR of 35% and aiming to a 50% RR for the experimental arm, 92 patients are to be enrolled in arm A and 46 patients in arm B. Estimating a rate of up to 8-10% of non-evaluable patients, enrolment can be extended up to 153 patients in total.