This phase I trial studies the side effects and best dose of capecitabine when given
together with oxaliplatin, leucovorin calcium, and fluorouracil in treating patients with
advanced cancer that is metastatic or cannot be removed by surgery. 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.
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.
- 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 (Common Toxicity Criteria [CTC] 2.0) neuropathy
- 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
- Breastfeeding should be discontinued if the mother is treated with oxaliplatin
- Ability to understand and the willingness to sign a written informed consent document
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
- 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
- Pregnant and nursing women are excluded from this study because oxaliplatin is a DNA
alkylating agent with the potential for teratogenic or abortifacient effects
- Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral
therapy (HAART) are excluded from the study