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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

April 25, 2008
May 9, 2011
March 2007
February 2009   (final data collection date for primary outcome measure)
Maximum tolerated dose of paclitaxel in combination with bortezomib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Maximum tolerated dose of paclitaxel in combination with bortezomib [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00667641 on ClinicalTrials.gov Archive Site
Not Provided
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Tumor response [ Designated as safety issue: No ]
  • Bim upregulation in peripheral blood mononuclear cells [ Designated as safety issue: No ]
  • Correlation of markers of Ras/Raf/MAPK pathway activation in fresh or archived tumor tissue with clinical response [ Designated as safety issue: No ]
  • Pharmacokinetics [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Paclitaxel and Bortezomib in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors
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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Starting dose level 0.70mg/m2
  • Drug: paclitaxel
    Starting dose level 40mg/m2
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
February 2009
February 2009   (final data collection date for primary outcome measure)

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®)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00667641
CDR0000592905, P30CA072720, CINJ-050608, MILLENNIUM-CINJ-050608, CINJ-IRB-0220060270
Yes
Vassiliki Karantza-Wadsworth, MD, PhD, UMDNJ/CINJ
University of Medicine and Dentistry of New Jersey
National Cancer Institute (NCI)
Principal Investigator: Vassil Karantza-Wadsworth, MD Rutgers Cancer Institute of New Jersey
Rutgers, The State University of New Jersey
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP