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

Primary Purpose

Breast Cancer, Colorectal Cancer, Head and Neck Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bortezomib
paclitaxel
Sponsored by
University of Medicine and Dentistry of New Jersey
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring unspecified adult solid tumor, protocol specific, recurrent breast cancer, stage IV breast cancer, recurrent prostate cancer, stage IV prostate cancer, recurrent colon cancer, stage IV colon cancer, recurrent pancreatic cancer, stage IV pancreatic cancer, recurrent ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, recurrent non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent melanoma, stage IV melanoma, stage IV papillary thyroid cancer, recurrent thyroid cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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®)

Sites / Locations

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Outcomes

Primary Outcome Measures

Maximum tolerated dose of paclitaxel in combination with bortezomib

Secondary Outcome Measures

Full Information

First Posted
April 25, 2008
Last Updated
May 9, 2011
Sponsor
University of Medicine and Dentistry of New Jersey
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00667641
Brief Title
Paclitaxel and Bortezomib in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors
Official Title
Phase I Study of Paclitaxel (Taxol) and Bortezomib (Velcade) in Patients With Refractory Solid Tumor Malignancies Involving an Activated MAPK Pathway
Study Type
Interventional

2. Study Status

Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Medicine and Dentistry of New Jersey
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Colorectal Cancer, Head and Neck Cancer, Lung Cancer, Melanoma (Skin), Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
unspecified adult solid tumor, protocol specific, recurrent breast cancer, stage IV breast cancer, recurrent prostate cancer, stage IV prostate cancer, recurrent colon cancer, stage IV colon cancer, recurrent pancreatic cancer, stage IV pancreatic cancer, recurrent ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, recurrent non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent melanoma, stage IV melanoma, stage IV papillary thyroid cancer, recurrent thyroid cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Description
Starting dose level 0.70mg/m2
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
Starting dose level 40mg/m2
Primary Outcome Measure Information:
Title
Maximum tolerated dose of paclitaxel in combination with bortezomib
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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®)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vassil Karantza-Wadsworth, MD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.clinicaltrials.gov/ct2/show/NCT00667641
Description
Clinical trial summary from the National Cancer Institute's PDQ® database

Learn more about this trial

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

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