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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT00667641
First received: April 25, 2008
Last updated: May 9, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Colorectal Cancer
Head and Neck Cancer
Lung Cancer
Melanoma (Skin)
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Drug: paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Paclitaxel (Taxol) and Bortezomib (Velcade) in Patients With Refractory Solid Tumor Malignancies Involving an Activated MAPK Pathway

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Maximum tolerated dose of paclitaxel in combination with bortezomib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 16
Study Start Date: March 2007
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: bortezomib
    Starting dose level 0.70mg/m2
    Drug: paclitaxel
    Starting dose level 40mg/m2
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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®)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667641

Locations
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
University of Medicine and Dentistry New Jersey
Investigators
Principal Investigator: Vassil Karantza-Wadsworth, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Vassiliki Karantza-Wadsworth, MD, PhD, UMDNJ/CINJ
ClinicalTrials.gov Identifier: NCT00667641     History of Changes
Other Study ID Numbers: CDR0000592905, P30CA072720, CINJ-050608, MILLENNIUM-CINJ-050608, CINJ-IRB-0220060270
Study First Received: April 25, 2008
Last Updated: May 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Rutgers, The State University of New Jersey:
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

Additional relevant MeSH terms:
Breast Neoplasms
Colorectal Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Melanoma
Ovarian Neoplasms
Pancreatic Neoplasms
Prostatic Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 17, 2014