Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study of Nab-Paclitaxel (Nanoparticle Albumin Bound-Paclitaxel) in Patients With Advanced Solid Tumors
- To develop a population pharmacokinetic model for paclitaxel administered as paclitaxel
albumin-stabilized nanoparticle formulation (nab-paclitaxel) to a large population of
patients with advanced or refractory cancer to characterize the inter-individual
pharmacokinetic variability of this agent.
- To explore nab-paclitaxel pharmacokinetic parameters in patients with metastatic
prostate cancer (castrate), metastatic breast cancer, advanced non-small cell lung
cancer and other incurable advanced or refractory tumors amenable to treatment with
- To explore the association between exposure to total and unbound paclitaxel after
administration of nab-paclitaxel and neutropenia.
- To explore the association between the CYP2C8*3 variant and paclitaxel clearance.
- To explore the association between other variants of CYP2C8 and other genes involved in
paclitaxel disposition including CYP3A4, CYP3A5, SLCO1B3 (OATP8), and ABCB1 (MDR1) and
paclitaxel pharmacokinetic parameters and toxicity after one course of treatment.
OUTLINE: This is a multicenter study.
Patients receive paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) IV
over 30 minutes on days 1, 8, 15, 22, 29, 36, 43, and 50. Treatment may repeat off study
every 9 weeks in the absence of disease progression or unacceptable toxicity.
Serial blood samplings are obtained at specified time points during course 1 including
baseline and days 1 and 8 of course 1 for pharmacokinetic studies. Samples are also examined
for genotype by PCR including variant genotypes in 2C8, CYP3A4, CYP3A5, ABCB1, ABCC2, ABCC10
and OATP1B3 genes.
Masking: Open Label, Primary Purpose: Treatment
Inter-individual pharmacokinetic variability
Sridhar Mani, MD
Albert Einstein College of Medicine of Yeshiva University