8 continuous vs 8 intermittent cycles in first and second line in her2/neu neg metastatic breast cancer

Conditions: Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Metastatic Breast Cancer

Summary: an open randomized phase iii study to compare 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy in first line treatment, in combination with bevacizumab, and second line treatment of patients with her2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.

the primary goal of this non-inferiority trial is to determine if the results obtained with a intermittent chemotherapy regimen (2 x 4 cycles of paclitaxel) are not inferior to the results of a continuous chemotherapy regimen (8 cycles of paclitaxel), both combined with bevacizumab in first line treatment of patients with her2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.

Eligibility criteria:
inclusion criteria: * female patients ≥ 18 years old. * patients with her2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer, who are candidates for chemotherapy. * patients with measurable or evaluable-only (recist 1.1) * documented estrogen receptor (er) / progesteron receptor (pr) status. * her2/neu-negative disease * patients with an ecog performance status ≤ 2. * life expectancy of \> 12 weeks. * signature of informed consent form exclusion criteria: * previous chemotherapy for her2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer. * prior hormonal therapy for her2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer that has not been discontinued 1 week before start of study treatment. * prior adjuvant/neo-adjuvant chemotherapy within 6 months prior to first study treatment. however, if the prior adjuvant/neo-adjuvant chemotherapy was taxane based, patients are excluded if they received their last chemotherapy within12 months prior to first study treatment. * prior radiotherapy covering more than 30% of marrow-bearing bone. * patients that have received recent radiation therapy that are not recovered from any significant (grade ≥ 3) acute toxicity prior to study treatment. * prior therapy with bevacizumab, sorafenib, sunitinib, or other vegf pathway-targeted therapy. * chronic daily treatment with aspirin * chronic daily treatment with corticosteroids, with the exception of inhaled steroids. * current or recent treatment with another investigational drug or participation in another investigational study. * inadequate bone marrow, liver, renal function * inr \> 1.5 or an aptt \> 1.5 x uln within 7 days prior to first study treatment. * known cns disease, except for treated brain metastases. * patients with concurrent active malignancy * pregnant or lactating * women of childbearing potential not using effective, non-hormonal means of contraception * major surgical procedure (including open biopsy) within 28 days prior to the first study treatment * core biopsy or other minor surgical procedure, within 7 days prior to day 1. * significant vascular disease within 6 months prior to day 1. * any previous venous thrombo-embolism \> ctc grade 3. * history of haemoptysis * history or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. * uncontrolled hypertension * clinically significant (i.e. active) cardiovasculair disease * lvef by muga or echo \< 50%. * history of abdominal fistula, grade 4 bowel obstruction or gi perforation, intra-abdominal abscess within 6 months of randomization. * serious non-healing wound, peptic ulcer or bone fracture. * known hypersensitivity to any of the study drugs or excipients. * hypersensitivity to chinese hamster ovary cell products or other recombinant human or humanized antibodies. * psychiatric illness, physical examination or laboratory findings that may interfer with protocol

Keywords: metastatic breast cancer her2/neu negative paclitaxel bevacizumab liposomal doxorubicine capecitabine