Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced or Refractory Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This clinical trial is studying how well paclitaxel albumin-stabilized nanoparticle formulation works in treating patients with advanced or refractory solid tumors.
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Procedure: gene expression analysis
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Procedure: polymerase chain reaction
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study of Nab-Paclitaxel (Nanoparticle Albumin Bound-Paclitaxel) in Patients With Advanced Solid Tumors|
- Inter-individual pharmacokinetic variability [ Designated as safety issue: No ]
- Pharmacokinetic parameters [ Designated as safety issue: No ]
- Neutropenia [ Designated as safety issue: No ]
- CYP2C8*3 variant expression [ Designated as safety issue: No ]
- Genetic variance relating to pharmacokinetics and toxicity [ Designated as safety issue: Yes ]
|Study Start Date:||September 2006|
|Estimated Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
- 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 nab-paclitaxel.
- 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.
|Study Chair:||Sridhar Mani, MD||Albert Einstein College of Medicine of Yeshiva University|