Phase I Study of Paclitaxel (Taxol) and Bortezomib (Velcade) in Patients With Refractory Solid Tumor Malignancies Involving an Activated MAPK Pathway
- To identify the maximum tolerated dose of paclitaxel in combination with bortezomib in
patients with metastatic or unresectable solid tumor malignancies that involve an
activated Ras/Raf/MAPK pathway.
- To assess the toxicity of this regimen.
- To assess tumor response in these patients.
- To determine whether Bim is upregulated in peripheral blood mononuclear cells obtained
from patients treated with this regimen.
- To correlate markers of Ras/Raf/MAPK pathway activation in fresh or archived tumor
tissue with clinical response in these patients.
- To perform pharmacokinetic (PK) studies to determine whether bortezomib alters
paclitaxel PK parameters.
OUTLINE: Patients receive paclitaxel IV over 1 hour and bortezomib IV on days 1, 8, and 15.
Treatment repeats every 21 days in the absence of disease progression or unacceptable
Blood samples are collected at baseline and periodically during course 1 for pharmacokinetic
and biomarker studies. Blood samples are analyzed for plasma concentrations of paclitaxel by
high performance liquid chromatography and for Bim protein levels and phosphorylation status
by western blotting. Tumor tissue samples, if available, are analyzed to evaluate the
presence of an activated Ras/Raf/MAPK pathway. Tumor tissue samples are analyzed for Ras
and/or Raf mutations by nucleic acid extraction and direct sequencing; Ras and/or Raf
overexpression by western blotting; Ras activation assay; and/or phospho-ERK by western
blotting and IHC.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of paclitaxel in combination with bortezomib
Vassil Karantza-Wadsworth, MD
Cancer Institute of New Jersey
United States: Food and Drug Administration
|Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School||New Brunswick, New Jersey 08903|