Paclitaxel and Bortezomib in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors

Breast Cancer Clinical Trial

Official title: Phase I Study of Paclitaxel (Taxol) and Bortezomib (Velcade) in Patients With Refractory Solid Tumor Malignancies Involving an Activated MAPK Pathway

Status Completed

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel together with bortezomib may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of paclitaxel and bortezomib in treating patients with metastatic or unresectable malignant solid tumors.

Clinical Trial Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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 toxicity.

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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Cancer
• Melanoma (Skin)
• Ovarian Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Prostate Cancer
• Prostatic Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT00667641
• Study type: Interventional
• Source: Rutgers, The State University of New Jersey
• Status: Completed
• Phase: Phase 1
• Start date: March 2007
• Completion date: February 2009