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

Phase 1
18 Years
Not Enrolling
Breast Cancer, Colorectal Cancer, Head and Neck Cancer, Lung Cancer, Melanoma (Skin), Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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



- 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.


- 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

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.

Inclusion Criteria


- 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


- 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


- 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®)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of paclitaxel in combination with bortezomib

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Vassil Karantza-Wadsworth, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

February 2009

Related Keywords:

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



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