366TiPThe NAME trial: A direct comparison of oral navelbine given either classic or metronomic in metastatic HER2 neg breast cancer

Background: Navebine is an antineplastic agent that has shown afficacy in the treatment of a variety of solid tumors, including breast cancer. The drug can be given intriavenously, but also as oral tablet treatment. Preclinical studies, as well as clinical observations, suggest that the administration of small, frequent doses of chemotherapy (metronomic dosing) has an effect, not only on cancer cells, but also on endothelialcells in the tumor vasculature. By giving smaller, but more frekvent doses of the drug, higher dose intensity, without corresponding side effects, is optained. Whether treatment under the metronomic principle is superior to conventional treatment, has not yet been validated in the clinic, so this study is hoped to clarify this. Trial design: This is a investigator-initated, prospective randomized fase II, non-blinded multinational, multicentre study running in Denmark and Norway. 200 women diagnosed with HER2 neg metastatic breast cancer will be enroled. Patients are randomized to either: Arm A Clasical treatment: Navelbine Oral: Navelbine Oralâ: 60 mg/m² day 1, day 8 (and day 15), every three weeks for the first cycle. Hereafter 80 mg/m² day 1 and day 8, every three weeks for de following cycles. Or Arm B Metronomic treatment: Navelbine Oralâ: with 3 week cycles of daily doses of 30 mg. (Patients with body surface ≤ 1,54 m² or 65 Years or more start on 20 mg daily.) Treatment is given first or second line (chemotherapy). The primary Objectives is to evaluate the Disease Control Rate (CR + PR + SD, SD > 3 months) in the two arms. Secondary Objectives are to compare the duration of Disease Control, TTP, RR, DR and OS and side effects for the two regimens. Also Evaluation of the Global Health Status/QoL, on the basis of the EORTC QOL C30 questionnaire is made. Finally a translational study to explore the potential of biomarkers during metronomic therapy is performed.The patients will be treated until progression or to high toxicity, or until the patient wishes discontinuation. Clinical trial identification: EudraCT: 2016-002165-63. Health Board no: 2017040059. Approved by Research Ethics Commitee and Data Protection Agency June 2017. Legal entity responsible for the study: Sven Tyge Langkjer. Funding: The study is an investigator-initiated study, but financially supported by the pharmaceutical company Pierre Fabre. Disclosure: All authors have declared no conflicts of interest.