- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00098982
Bortezomib, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Advanced or Metastatic Colorectal Cancer
Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Naples, Italy, 80131
- Istituto Nazionale Per Lo Studio E La Cura Dei Tumori
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Lausanne, Switzerland, CH-1011
- Centre Hospitalier Universitaire Vaudois
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England
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Leeds, England, United Kingdom, LS9 7TF
- Leeds Cancer Centre at St. James's University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0
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Secondary Outcome Measures
Outcome Measure |
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Safety as measured by CTC v3.0
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Response as measured by RECIST every 8 weeks
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Time to progression as measured by Kaplan Meier and RECIST every 8 weeks
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Collaborators and Investigators
Investigators
- Study Chair: Francesco Caponigro, MD, Istituto Nazionale Per Lo Studio E La Cura Dei Tumori
Publications and helpful links
General Publications
- Caponigro F, Lacombe D, Twelves C, Bauer J, Govaerts AS, Marreaud S, Milano A, Anthoney A. An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer. Eur J Cancer. 2009 Jan;45(1):48-55. doi: 10.1016/j.ejca.2008.08.011. Epub 2008 Sep 20.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Micronutrients
- Vitamins
- Calcium-Regulating Hormones and Agents
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Oxaliplatin
- Leucovorin
- Calcium
- Levoleucovorin
- Bortezomib
Other Study ID Numbers
- EORTC-16029
- MILLENNIUM-EORTC-16029
- 2004-001763-21 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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