Pilot Study to Evaluate Safety & Biological Effects of Orally Administered Reparixin in Early Breast Cancer
Status:
Terminated
Trial end date:
2016-03-01
Target enrollment:
Participant gender:
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.