Phase I Study of Oxaliplatin in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction
N/A
N/A
Both
Liver Disease
Trial Information
Phase I Study of Oxaliplatin in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction
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.
Inclusion Criteria
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
marrow.
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
institutional normal.
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
oxaliplatin.
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
arrhythmia.
No HIV-positive patients receiving anti-retroviral therapy (HAART).
No known allergy to erythromycin or indocyanine green.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Authority:
United States: Federal Government
Study ID:
000172
NCT ID:
NCT00006062
Start Date:
July 2000
Completion Date:
May 2001
Related Keywords:
- Liver Disease
- Liver Impairment
- Pharmacokinetics
- Platinum Analogues
- Liver Diseases
Name | Location |
|---|---|
| National Cancer Institute (NCI) | Bethesda, Maryland 20892 |
