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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00098982
First received: December 8, 2004
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Colorectal Cancer
Drug: bortezomib
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety as measured by CTC v3.0 [ Designated as safety issue: Yes ]
  • Response as measured by RECIST every 8 weeks [ Designated as safety issue: No ]
  • Time to progression as measured by Kaplan Meier and RECIST every 8 weeks [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: September 2004
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

PROJECTED ACCRUAL: Not specified.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

  • 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)

Renal

  • Creatinine ≤ 1.7 mg/dL

Cardiovascular

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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

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

Endocrine therapy

  • Not specified

Radiotherapy

  • More than 4 weeks since prior radiotherapy

Surgery

  • More than 14 days since prior major surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098982

Locations
Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori
Naples, Italy, 80131
Switzerland
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
Investigators
Study Chair: Francesco Caponigro, MD Istituto Nazionale per lo Studio e la Cura dei Tumori
  More Information

Additional Information:
Publications:
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, EORTC-16029, MILLENNIUM-EORTC-16029, 2004-001763-21
Study First Received: December 8, 2004
Last Updated: June 11, 2013
Health Authority: United States: Federal Government

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
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Bortezomib
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on August 26, 2014