Pilot Study to Evaluate Safety & Biological Effects of Orally Administered Reparixin in Early Breast Cancer

Summary

This is a pilot "window of opportunity" clinical study in patients with operable breast cancer investigating use of reparixin as single agent in the time period between clinical diagnosis and surgery. The primary objectives of this study were: 1- to evaluate the effects of orally administered reparixin on CSCs in the primary tumor and the tumoral microenvironment in an early breast cancer population: A. CSC were measured in tissue samples by techniques that could include: ALDEFLUOR assay and assessment of CD44/CD24 by flow cytometry, or examination of RNA transcripts by RT-PCR, aldehyde dehydrogenase-1, CD44/CD24 and epithelial mesenchymal transition markers (Snail, Twist, Notch) by immunohistochemistry (IHC). CSC were defined as ALDEFLUOR positive (ALDH-1+) and/or CD44 high/CD24 low by flow cytometry or RT-PCR and IHC and by the detection of ALDH-1+ cells with or without epithelial mesenchymal transition (EMT) transcription factor in IHC assays. B. Serine-threonine protein kinase (AKT), focal adhesion kinase (FAK), phosphatase and tensin homolog (PTEN) and chemokine receptor-1 (CXCR1) levels were measured in tissue samples by IHC. C. Measurement of markers of inflammation (interleukin-1beta \[IL-1β\], interleukin-6 \[IL-6\], interleukin-8 \[IL-8\], tumor necrosis factor-alpha \[TNF-α\], granulocyte macrophage colony stimulating factor \[GM-CSF\], vascular endothelial growth factor \[VEGF\], basic fibroblast growth factor \[b-FGF\] and high-sensitivity C-reactive protein \[hsCRP\]) in plasma, leukocyte subsets (enumerate T subsets, B, and natural killer/natural killer T \[NK/NKT\] cells) and study polymorphonuclear leukocyte \[PMN\] biology in peripheral blood samples. D. Measurement of markers of angiogenesis (CD31 staining), tumor-infiltrating leukocytes (CD4, CD8, NK and macrophages), autophagy (P62 and LC3 by IHC), EpCAM and EMT markers (CD326, CD45, Twist1, SNAIL1, SLUG, ZEB1, FOXC2, TG2, Akt2, P13k and CK19 by RT-PCR) and tissue cellularity (residual disease characterization in tumor bed) in tumor tissue samples. 2\. To evaluate the safety of oral reparixin administered three times daily (t.i.d.) for 21 consecutive days. The secondary objective was to define the pharmacokinetic (PK) profile of orally administered reparixin.

Timeline

Start

2013-02

Primary completion

2015-03

Completion

2016-03-01

Outcome

Outcome not reported

Stopped (Enrollment): “Enrollment target not reached”

Publications

• Cai S, Wei X, Li Q, Jiang Z, Li L. Smart materials in pharmacological drug development: Neutrophils and its constituents for drug delivery and consequent antitumor effects. Mol Immunol. 2025 Jul;183:18-32. doi: 10.1016/j.molimm.2025.04.010. Epub 2025 May 2.
• Goldstein LJ, Mansutti M, Levy C, Chang JC, Henry S, Fernandez-Perez I, Prausova J, Staroslawska E, Viale G, Butler B, McCanna S, Ruffini PA, Wicha MS, Schott AF; fRida Trial Investigators. A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida). Breast Cancer Res Treat. 2021 Nov;190(2):265-275. doi: 10.1007/s10549-021-06367-5. Epub 2021 Sep 3.
• Goldstein LJ, Perez RP, Yardley D, Han LK, Reuben JM, Gao H, McCanna S, Butler B, Ruffini PA, Liu Y, Rosato RR, Chang JC. A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer. Breast Cancer Res. 2020 Jan 10;22(1):4. doi: 10.1186/s13058-019-1243-8.

Drugs

Indications