Oxaliplatin to Treat Advanced Cancers With Liver Dysfunction
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.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||Phase I Study of Oxaliplatin in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction|
|Study Start Date:||July 2000|
|Estimated Study Completion Date:||May 2001|
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.
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|