Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0
Safety Issue:
Yes
Principal Investigator
Francesco Caponigro, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Istituto Nazionale per lo Studio e la Cura dei Tumori
Authority:
United States: Federal Government
Study ID:
EORTC-16029
NCT ID:
NCT00098982
Start Date:
September 2004
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage III colon cancer
- stage IV colon cancer
- stage III rectal cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
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