Trial Information

Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression

Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating
side effects of neurotoxic chemotherapy, and can significantly interfere with patient
quality of life (QOL) and the administration of antineoplastic therapy. There is no
currently approved safe and effective treatment for CIPN. This protocol will explore the
molecular-genetic mechanisms associated with the natural history of CIPN progression by (1)
identification of differentially expressed genes and proteins as biomarkers for the onset of
CIPN; (2) evaluation of the relationship between biomarkers and the severity of CIPN during
the observation period, and (3) determining the relationship between molecular-genetic
biomarkers, morphological changes in small nerve fiber and the severity of neuropathic
symptoms.

Study population: Cancer patients who plan to receive chemotherapy treatment with either
taxane class, vinca alkaloid class, platinum compounds or bortezomib.

Design: This is a prospective, exploratory, natural history study to identify the
molecular-genetic mechanisms involved in chemotherapy-induced neuropathy in cancer patients.
A physician-based neuropathy scale, patient neurotoxocity questionnaire, and the total
neuropathy score will be used to measure the severity of peripheral neuropathy at baseline
and after completion of each cycle of chemotherapy infusion. Whole peripheral blood and skin
biopsy (only from patients who consent to biopsies) will be collected at baseline and after
a subsequent infusion cycle to evaluate gene/protein expression and immunohistochemical
labeling at peripheral sites of neuropathic injury. Microarray gene expression analysis will
be employed to identify differential regulation of genes involved in the development of CIPN
at the different time points compared with gene expression from the baseline samples. Genes
of interest will be validated by qRT-PCR to identify novel pharmacological targets to be
evaluated in future prospective studies. Protein levels corresponding to the changes in gene
expression will be evaluated using ELISA and verified by Western blotting.

Outcome measures: The primary outcome of the study will be the changes in gene and protein
expression in the peripheral blood and skin biopsy among cancer patients undergoing
chemotherapy. The secondary outcome will be the relationship between the molecular-genetic
biomarkers identified and the presence of peripheral neuropathic symptoms and their impacts
on patient's QOL.