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Bortezomib, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Advanced or Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00098982
Recruitment Status : Completed
First Posted : December 9, 2004
Last Update Posted : June 12, 2013
Information provided by (Responsible Party):

Study Description
Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, 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. It may also help the chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Giving bortezomib with fluorouracil, leucovorin, and oxaliplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given with fluorouracil, leucovorin, and oxaliplatin in treating patients with advanced or metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: bortezomib Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Phase 1

Detailed Description:



  • Determine the dose-limiting toxicity and maximum tolerated dose of bortezomib when administered with fluorouracil, leucovorin calcium, and oxaliplatin in patients with advanced or metastatic colorectal cancer.
  • Determine the recommended phase II dose of bortezomib in patients treated with this regimen.


  • Determine response in patients with measurable disease treated with this regimen.

OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of bortezomib.

Patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15; oxaliplatin IV over 2 hours on days 1 and 15; and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients receive treatment at the MTD to a maximum of 12 patients at that dose level.

Patients are followed every 8 weeks until disease progression or start of a new anticancer treatment.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer
Study Start Date : September 2004
Primary Completion Date : January 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :
  1. Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0

Secondary Outcome Measures :
  1. Safety as measured by CTC v3.0
  2. Response as measured by RECIST every 8 weeks
  3. Time to progression as measured by Kaplan Meier and RECIST every 8 weeks

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed advanced or metastatic colorectal cancer
  • Amenable to first-line treatment with oxaliplatin, fluorouracil, and leucovorin calcium for advanced or metastatic disease
  • No symptomatic or radiologic evidence of brain metastases



  • Over 18

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified


  • Absolute neutrophil count ≥ 2,000/mm^3
  • Platelet count ≥ 100,000/mm^3


  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
  • AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)


  • Creatinine ≤ 1.7 mg/dL


  • No ischemic heart disease within the past 6 months
  • No clinically significant ECG changes


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No baseline neuropathy > grade 1
  • No other prior or concurrent malignancy except cone-biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
  • No unstable systemic disease
  • No active uncontrolled infection
  • No psychological, familial, sociological, or geographical condition that would preclude study participation
  • No hypersensitivity to bortezomib, boron, or mannitol


Biologic therapy

  • Not specified


  • No prior oxaliplatin
  • No prior chemotherapy for advanced or metastatic disease
  • At least 6 months since prior adjuvant chemotherapy

Endocrine therapy

  • Not specified


  • More than 4 weeks since prior radiotherapy


  • More than 14 days since prior major surgery
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00098982

Istituto Nazionale per lo Studio e la Cura dei Tumori
Naples, Italy, 80131
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Study Chair: Francesco Caponigro, MD Istituto Nazionale per lo Studio e la Cura dei Tumori
More Information

Lacombe DA, Caponigro F, Anthoney A, et al.: A phase I study of bortezomib in combination with 5FU/LV plus oxaliplatin in patients (pts) with advanced colorectal cancer (CRC): EORTC 16029. [Abstract] J Clin Oncol 25 (Suppl 18): A-4090, 2007.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00098982     History of Changes
Other Study ID Numbers: EORTC-16029
2004-001763-21 ( EudraCT Number )
First Posted: December 9, 2004    Key Record Dates
Last Update Posted: June 12, 2013
Last Verified: June 2013

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents