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A Phase I Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in Combination With Oral Capecitabine in Patients With Advanced Malignancy

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in Combination With Oral Capecitabine in Patients With Advanced Malignancy


I. To establish the MTD and toxicity profile of oral capecitabine in combination with q 2
weekly intravenous oxaliplatin in patients with advanced malignancies.


I. To characterize the pharmacokinetic parameters of capecitabine at the recommended phase
II dose for combinations of capecitabine, oxaliplatin, 5-fluorouracil, and leucovorin, as
well as for the combination of capecitabine and oxaliplatin.

II. To observe for and record any antitumor activity.

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

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed malignancy which is
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effective

- There is no limit on prior therapies

- ECOG performance status 0-2

- Leukocytes >= 3,000/ul

- Absolute neutrophil count >= 1,500/ul

- Platelets >= 100,000/ul

- Total bilirubin =< 1.5 mg/dL

- AST (SGOT)/ALT (SGPT) =< 2.5 x institutional upper limit of normal

- Creatinine clearance >= 50 mL/min as calculated by the Cockroft-Gault formula

- Patients with no >= grade 2 (CTC 2.0) neuropathy

- The effects of oxaliplatin on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason and because DNA alkylating agents are
known to be teratogenic, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control) prior to study
entry and for the duration of study participation; should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately

- Because the risk of toxicity in nursing infants secondary to oxaliplatin treatment of
the mother is unknown but may be harmful, breastfeeding should be discontinued if the
mother is treated with oxaliplatin

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study

- Patients undergoing therapy with other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other toxicities

- History of allergy to platinum compounds or to antiemetics appropriate for
administration in conjunction with protocol-directed chemotherapy

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, or unstable angina pectoris, or
cardiac arrhythmia

- Pregnant and nursing women are excluded from this study because oxaliplatin is a DNA
alkylating agent with the potential for teratogenic or abortifacient effects

- HIV-positive patients receiving anti-retroviral therapy (HAART) are excluded from the
study because of possible pharmacokinetic interactions

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD, defined as the highest dose level which results in DLT in fewer than 2/6 patients, graded according to the NCI CTC version 2.0

Outcome Time Frame:

Up to 28 days

Safety Issue:


Principal Investigator

Daniel Mulkerin

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Wisconsin Hospital and Clinics


United States: Food and Drug Administration

Study ID:




Start Date:

June 2002

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001