Oxaliplatin to Treat Advanced Cancers With Liver Dysfunction

NCT00006062 | Completed Phase 1

• 2 other identifiers: 00017200-C-0172
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Liver Disease

Keywords

Liver Impairment; Pharmacokinetics; Platinum Analogues

Interventions

oxaliplatin DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kraker AJ, Moore CW. Accumulation of cis-diamminedichloroplatinum(II) and platinum analogues by platinum-resistant murine leukemia cells in vitro. Cancer Res. 1988 Jan 1;48(1):9-13.

  PMID: 3335002 BACKGROUND

• Pendyala L, Creaven PJ. In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin. Cancer Res. 1993 Dec 15;53(24):5970-6.

  PMID: 8261411 BACKGROUND

• Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, Fojo T. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's Anticancer Drug Screen panel. Biochem Pharmacol. 1996 Dec 24;52(12):1855-65. doi: 10.1016/s0006-2952(97)81490-6.

  PMID: 8951344 BACKGROUND

MeSH Terms

Conditions

Liver Diseases

Interventions

Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 11, 2000
• First Posted: December 10, 2002
• Study Start: July 1, 2000
• Study Completion: May 1, 2001
• Last Updated: March 4, 2008

Record last verified: 2000-06

Locations

US (1)