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

Phase 1

Completed

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

• Registration Number: NCT00667641
• Lead Sponsor: University of Medicine and Dentistry of New Jersey

Brief 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.

Detailed 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 Timeline

• Study Start: 2007-03
• Study First Submitted: 2008-04-25
• Study First Submitted QC: 2008-04-25
• Study First Posted: 2008-04-28
• Primary Completion: 2009-02
• Study Completion: 2009-02
• Status Verified: 2011-05
• Last Update Submitted: 2011-05-09
• Last Update Posted: 2011-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of paclitaxel in combination with bortezomib	2 years

Trial Locations

Locations (1)

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School; 🇺🇸 New Brunswick, New Jersey, United States