Phase Ib Pilot Study to Evaluate Reparixin in Combination with Weekly Paclitaxel in Patients with HER-2-Negative Metastatic Breast Cancer

Clin Cancer Res. 2017 Sep 15;23(18):5358-5365. doi: 10.1158/1078-0432.CCR-16-2748. Epub 2017 May 24.


Purpose: Chemokine receptor 1 (CXCR1) is recognized as an actionable receptor selectively expressed by breast cancer stem cells (BCSCs). Reparixin is an investigational allosteric inhibitor of chemokine receptors 1 and 2 (CXCR1/2), and demonstrates activity against BCSCs in human breast cancer xenografts. This phase Ib clinical trial examined dose, safety, and pharmacokinetics of paclitaxel plus reparixin therapy, and explored effects of reparixin on BCSCs in patients with metastatic breast cancer (MBC) (trial registration ID: NCT02001974).Experimental Design: Eligible patients had MBC and were candidates for paclitaxel therapy. Study treatment included a 3-day run-in with reparixin oral tablets three times a day, followed by paclitaxel 80 mg/m2/week (days 1, 8, and 15 for 28-day cycle) + reparixin tablets three times a day for 21/28 days; three dose cohorts were examined in a 3+3 dose escalation schema. Additional patients were recruited into an expansion cohort at the recommended phase II dose to further explore pharmacokinetics, safety, and biological effects of the combination therapy.Results: There were neither G4-5 adverse events nor serious adverse events related to study therapy and no interactions between reparixin and paclitaxel to influence their respective pharmacokinetic profiles. A 30% response rate was recorded, with durable responses >12 months in two patients. Exploratory biomarker analysis was inconclusive for therapy effect on BCSCs.Conclusions: Weekly paclitaxel plus reparixin in MBC appeared to be safe and tolerable, with demonstrated responses in the enrolled population. Dose level 3, 1200 mg orally three times a day, was selected for further study in a randomized phase II trial (NCT02370238). Clin Cancer Res; 23(18); 5358-65. ©2017 AACR.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Combined Modality Therapy
  • Female
  • Humans
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacokinetics
  • Pilot Projects
  • Receptor, ErbB-2 / metabolism
  • Receptors, Interleukin-8A / antagonists & inhibitors
  • Retreatment
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacokinetics
  • Treatment Outcome


  • Biomarkers, Tumor
  • Receptors, Interleukin-8A
  • Sulfonamides
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel
  • reparixin

Associated data