Liver DiseasePhase 1NCT00006062
Oxaliplatin to Treat Advanced Cancers With Liver Dysfunction
A Phase 1 study testing oxaliplatin in people with Liver Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Liver Disease
- What is being tested?
- oxaliplatin
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2000to May 2001
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: Phase I Study of Oxaliplatin in Patients With Advanced Malignancies and Varying Degrees of 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.
Read more
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.
Read the detailed description
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.
- Conditions
- Liver Disease
- Being tested
- oxaliplatin
- Keywords
- Liver Impairment, Pharmacokinetics, Platinum Analogues
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oxaliplatinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startJul 2000
- Study completionMay 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Liver DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 60 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006062
- Sponsor's protocol ID
- 000172
- Other IDs
- 00-C-0172
- Status last verified
- Jun 2000
- First submitted
- 11 Jul 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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.
PubMed 3335002Pendyala 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.
PubMed 8261411Rixe 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.
PubMed 8951344
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Oxaliplatin in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction
- ClinicalTrials.gov ID
- NCT00006062
- Acronym / sponsor ID
- 000172
- Conditions
- Liver Disease
- Keywords
- Liver Impairment, Pharmacokinetics, Platinum Analogues
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2000
- Study completion
- May 2001
- First posted
- 10 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oxaliplatin | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 3335002Kraker 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.
- Background: PubMed 8261411Pendyala 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.
- Background: PubMed 8951344Rixe 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.
Related trials for Liver Disease
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruitingObservational study
Periodontal Status and Biomarkers in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing oxaliplatin in people with Liver Disease, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006062, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.