RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining oxaliplatin, fluorouracil, leucovorin, and capecitabine in treating patients who have advanced cancer.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: capecitabine  Drug: fluorouracil  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose (MTD) of capecitabine when administered with oxaliplatin, fluorouracil, and leucovorin calcium, as well as the MTD of capecitabine combined with oxaliplatin alone, in patients with advanced malignancies.
• Determine the toxicity profile of these regimens in these patients.

Secondary

• Determine the pharmacokinetic parameters of capecitabine at the recommended phase II dose of these regimens in these patients.
• Determine any antitumor activity of these regimens in these patients.

OUTLINE: This is a dose-escalation study of capecitabine.

Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV on days 1 and 15. Patients also receive oral capecitabine every 8 hours on days 1-2 and 15-16. Leucovorin calcium and fluorouracil administration is held at dose level 4 and above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 additional patients are accrued to receive treatment at the recommended phase II dose.

PROJECTED ACCRUAL: A total of 40-50 patients will be accrued for this study within 2-2.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignancy
• Metastatic or unresectable disease for which standard curative or palliative therapy does not exist or is no longer effective
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• No history of allergy to platinum compounds or antiemetics used in this study
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No evidence of neuropathy greater than grade 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• Any prior therapy allowed
• No other concurrent investigational agents
• No concurrent anti-retroviral therapy for HIV-positive patients
• No other concurrent commercial agents or therapies for the malignancy

Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States; Recruiting

Study chairs or principal investigators

Daniel Mulkerin, MD,  Study Chair,  University of Wisconsin Comprehensive Cancer Center   

Study ID Numbers:  CDR0000256335; WCCC-CO-02901; NCI-5904; NCT00043121
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  August 5, 2002
ClinicalTrials.gov Identifier:  NCT00043121
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08