A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer

The Objectives of this study: The primary objective of the study was to evaluate progression-free survival (PFS) (defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occured first) in patients with metastatic triple-negative breast cancer (TNBC) treated with the combination of paclitaxel and orally administered reparixin compared to paclitaxel alone. The secondary objectives were: * To determine overall survival (OS). * To evaluate objective response rates (ORR). * To determine median PFS (mPFS). * To assess the safety of the combination of paclitaxel and orally administered reparixin (referred to as combination treatment).

The study is a two arm, phase 2 study to evaluate the efficacy of the combination of paclitaxel and reparixin compared to paclitaxel and placebo in metastatic TNBC patients. In the study two groups There were two groups: Group 1: paclitaxel 80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle) + reparixin oral tablets 1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21. Group 2: paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + placebo oral tablets 1200 mg t.i.d. continuing from Day 1 to Day 21. Study drug (reparixin/placebo) was administered with water prior to the start of the i.v. paclitaxel infusion on Cycle 1, Day 1 and then administered approximately every eight hours (six to ten hours) for 21 consecutive days during each cycle with seven days off-treatment between each cycle. It was preferable that reparixin was taken with food. However, if the patient was unable to eat, study drug was allowed to be administered. When in combination with paclitaxel (Day 1, 8 and 15 of each cycle), reparixin or placebo was administered every approximately eight hours with about 250 mL water and a light meal or snack. Paclitaxel was administered in combination with study drug (reparixin/placebo) as an i.v. infusion on Days 1, 8 and 15 of each 28-day cycle. On Cycle 1, Day 1, paclitaxel was administered at the clinic after the administration of study drug (reparixin/placebo). From that point forward, study drug (reparixin/placebo) was self-administered t.i.d. for 21 days. Combination treatment (three weeks on and one week off) continued until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. The next clinic visits were on Days 8 and 15 when a paclitaxel infusion was administered to the patient. The patients returned to the clinic again on Day 29/Day 1 of the next cycle. Tumor response and/or progression assessments were performed and documented every eight weeks according to RECIST criteria version 1.1. Metastatic tissue samples were analyzed for evaluation of CD24-CD44+ and aldehyde dehydrogenase positive (ALDH+) CSCs.