This is a phase I study of the experimental anticancer drug oxaliplatin. It is designed to
establish the maximum dose of the drug that can be given safely to patients with cancer who
have impaired liver function and to determine the drug's side effects. It will also examine
how liver function affects the drug's elimination from the body. The liver plays an
important role in the elimination of many anticancer drugs, and patients with impaired liver
function should not take certain drugs or should take them in reduced doses.
Patients 18 years of age and older with cancer that has metastasized (spread from the
original tumor site) and for whom standard treatment is not available or is no longer
effective may be eligible for this study. Candidates will be screened with various tests
and procedures that may include physical examination, computerized tomography (CT) or
magnetic resonance imaging (MRI) scans, chest X-rays, and blood and urine tests.
Participants will be given oxaliplatin in doses determined according to their level of liver
function. Patients may have normal liver function or mildly, moderately or severely
impaired liver function, or may have had a liver transplant. Oxaliplatin will be infused
intravenously (through a vein) over two hours on the first day of 21-day treatment
cycles-that is, once every 3 weeks. Treatment will continue as long as the cancer is under
control and side effects do not require stopping the drug. Urine will be collected over 48
hours after the infusion to determine how much of the drug is eliminated in urine. Blood
tests will be done to monitor safety of the treatment, and imaging studies, such as X-rays,
CT and MRI scans, will be done periodically to evaluate the tumor's response to treatment.
Special blood tests will also be done to study how oxaliplatin is eliminated from the body.
With the first dose of the drug, blood samples will be collected just before the infusion
begins, just before it ends, 15 minutes, 30 minutes, 1, 2, 4, 6, 24, 48, and 72 hours after
the infusion, and again 1 week and 3 weeks later. Additional blood samples may be collected
at the third treatment cycle.
Oxaliplatin is a diaminocyclohexane platinum derivative with known anticancer activity in
solid tumors. The recommended single-agent dose of oxaliplatin in adult cancer patients is
130 mg/m(2) given intravenously over 2 hours every 3 weeks. Hepatic metabolism is the major
route of drug elimination for many anti-cancer agents. Although there is limited safety and
pharmacokinetic data for oxaliplatin in patients with renal impairment, there is currently
no data regarding its disposition in patients with liver dysfunction. This phase I and
pharmacologic study of a single agent oxaliplatin is being conducted in adult cancer
patients with advanced malignancies and varying degrees of liver dysfunction. Patients will
be stratified into five groups based upon their degree of liver dysfunction as assessed by
liver function tests. Group A will consist of patients with normal hepatic function to
serve as pharmacologic controls. Group E will consist of patients who have received a liver
transplant. The remaining 3 groups will start at different doses of oxaliplatin based on
hepatic dysfunction and dose escalation in these groups will proceed in a manner in
accordance with standard phase I trial with 3 patients per dose level until dose limiting
toxicity is observed. Pharmacokinetic monitoring will be performed in all patients on
study. The goals of this trial are to define the toxicities and pharmacokinetics of single
agent oxaliplatin in this patient population and to determine recommended doses of
oxaliplatin in patients with different degrees of hepatic impairment.
Must have histologically confirmed malignancy which is metastatic or unresectable and for
which standard curative or palliative treatments do not exist or are no longer effective.
Must have had 3 or fewer previous regimens (may have included prior platinum therapy).
Previous radiation allowed but should have included less than or equal to 30% of bone
At least 18 years old.
Karnofsky performance status greater than or equal to 60%. Patients should have an
expected survival of at least 2 months.
Leukocytes greater than or equal to 3,000/micro liter; or absolute neutrophil count
greater than or equal to 1,500/micro liter; or platelets greater than or equal to
100,000/micro liter, creatinine within normal institutional limits; or measured creatinine
clearance greater than or equal to 60 mL/min for patients with creatinine levels above
Abnormal liver function is acceptable.
Biliary obstruction for which a shunt has been placed is acceptable provided the shunt is
in place for at least 10 days prior to the first dose of oxaliplatin to allow the liver
function tests to stabilize.
No evidence of clinically significant neuropathy.
Women of childbearing 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. Breastfeeding should be discontinued if the mother is treated with
Must be able to understand and willing to sign a written informed consent document.
No chemotherapy or radiotherapy within 4 weeks prior to entering the study and no platinum
therapy within 6 weeks prior to entering the study.
Not undergoing therapy with other investigational agents.
No known brain metastases.
No history of allergy to platinum compounds or to antiemetics appropriate for
administration in conjunction with protocol-directed chemotherapy.
No uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac
No HIV-positive patients receiving anti-retroviral therapy (HAART).
No known allergy to erythromycin or indocyanine green.