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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 1

Conditions

Colorectal Cancer

Treatments

Drug: bortezomib

Drug: leucovorin calcium

Drug: oxaliplatin

Drug: fluorouracil

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00098982

2004-001763-21 (EudraCT Number)

MILLENNIUM-EORTC-16029

EORTC-16029

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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