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

May 9, 2011 updated by: University of Medicine and Dentistry of New Jersey

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- New Jersey
  - New Brunswick, New Jersey, United States, 08903
    - Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Histologically confirmed malignant solid tumor that involves an activated Ras/Raf/MAPK pathway, including the following:
- Breast cancer
- Prostate cancer
- Colon cancer
- Pancreatic cancer
- Ovarian cancer
- Non-small cell lung cancer
- Melanoma
- Papillary thyroid cancer
Metastatic or unresectable disease
Standard curative or palliative measures do not exist or are no longer effective
No newly diagnosed, untreated, or uncontrolled brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
ANC ≥ 1,500/μL
WBC ≥ 3,500/μL
Platelet count ≥ 100,000/μL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN for tumor involvement of the liver)
Creatinine ≤ 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No neuropathy ≥ grade 1 with pain within the past 14 days
No active infections
No myocardial infarction within the past 6 months
No NYHA class III or IV heart failure
No uncontrolled angina
No severe uncontrolled ventricular arrhythmias
No evidence of acute ischemia or active conduction system abnormalities by ECG
- Any ECG abnormality at screening must be documented by the investigator as not medically relevant
No hypersensitivity to bortezomib, boron, or mannitol
No serious medical or psychiatric illness likely to interfere with study participation

PRIOR CONCURRENT THERAPY:

Prior paclitaxel or bortezomib allowed
At least 4 weeks since prior chemotherapy and/or radiotherapy
More than 14 days since other prior investigational drugs
No other concurrent investigational agents
No other concurrent anticancer agents, including chemotherapy and biologic agents
No concurrent recombinant interleukin-11 (Neumega®)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose of paclitaxel in combination with bortezomib Time Frame: 2 years	2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Medicine and Dentistry of New Jersey

Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator: Vassil Karantza-Wadsworth, MD, Rutgers Cancer Institute of New Jersey

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)