NeoplasmsPhase 1NCT00674024
Pazopanib to Treat Adults With Advanced Cancers and Varying Degrees of Liver Function
A Phase 1 study testing Pazopanib and Pazopanib (GW786034)(GW786034) in people with Neoplasms and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Pazopanib is an experimental drug that was designed to enter cancer cells and block the activity of proteins that are important for cancer cell growth and survival. This is the first study in which pazopanib is given to patients with different degrees of liver function. Read more about this study
- Who is it for?
- Ages 18 to 110 years
- What is being tested?
- Pazopanib and Pazopanib (GW786034)(GW786034)
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2008to 22 Jan 2013
- 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 18 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For patients at the NCI, histological or cytological confirmation of solid tumor or lymphoma diagnosis will be performed at the NCI Laboratory of Pathology.
Who cannot join
- Patients who have had prior treatment with pazopanib will not be eligible for this study.
- Patients with abnormal liver function except grade 4 AST, grade 4 ALT, and grade 4 bilirubin will be eligible and will be grouped according to the criteria in Section 5.1. For assessing hepatic dysfunction, greater than 35 percent of the total bilirubin must be direct bilirubin.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I and Pharmacokinetic Single Agent Study of Pazopanib in Adults With Advanced Malignancies and Varying Degrees of Liver Dysfunction
Background:
- Pazopanib is an experimental drug that was designed to enter cancer cells and block the activity of proteins that are important for cancer cell growth and survival.
- This is the first study in which pazopanib is given to patients with different degrees of liver function. The safe dose for patients with normal liver function is already known.
Read more
Objectives:
- To determine the safety and side effects of pazopanib given at different dose levels to patients with cancer who have different degrees of liver function.
- To find out how much pazopanib is in the blood at specific times.
- To determine if pazopanib is effective in treating advanced cancer in patients with different degrees of liver function.
Eligibility:
- Patients 18 years of age and older with an advanced solid tumor or lymphoma that cannot be treated successfully with standard therapies and who have normal or abnormal liver function.
Design:
- Treatment:
- Patients are divided into 4 groups, based on their liver function. The first three patients in each group receive a low dose of pazopanib. The next three in each group receive a higher dose of pazopanib if no serious side effects were reported in the previous three. The dose is increased in succeeding groups of three patients until the maximum study dose is reached.
- Patients take pazopanib once a day by mouth in 21-day treatment cycles. Treatment continues until the cancer worsens, the patient develops severe side effects, the patient no longer wants to continue the study, or the doctor removes the patient from the study for other reasons.
- Monitoring:
- Blood pressure: Patients monitor and record their blood pressure twice a day after starting treatment.
- Blood tests: Patients have weekly routine blood tests. In addition, at week 3 of the first cycle and again after the highest safe dose has been determined, several blood samples are collected at frequent intervals to determine how the body handles the drug.
- Imaging studies: X-rays or scans or both are done to measure the extent of disease every 3 cycles.
- Physical examinations are done at periodic intervals.
Read the detailed description
Background:
- Pazopanib is a potent, multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alpha, PDGFR-beta, and c-kit with the potential to inhibit angiogenesis, lymphangiogenesis, and tumor growth that may have an advantage over agents with a narrower kinase specificity profile.
- Pazopanib has shown activity in renal cell cancer with tumor shrinkage and stable disease; Phase I, II, and III trials as single therapy and in combination with lapatinib are ongoing or planned in patients with various solid tumors.
- Pazopanib appears to be well tolerated at doses from 50 mg three times weekly to 2000 mg daily; the most common adverse events are hypertension, diarrhea, nausea, fatigue, and hair depigmentation.
Objectives:
- To establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of pazopanib in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) in order to provide appropriate dosing recommendations for pazopanib in such patients.
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of pazopanib and metabolites (GSK1071306, GSK1268992, GSK1268997, and GW700201) in patients with varying degrees of hepatic dysfunction.
- To document the non-DLTs associated with administration of pazopanib in patients with hepatic dysfunction.
- To explore correlations of the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma PK, and PD of pazopanib administration.
- To document any antitumor activity associated with pazopanib treatment of patients enrolled on this study.
Eligibility:
- Adult patients must have histologically or cytologically confirmed solid tumor or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must have adequate renal and bone marrow function.
Study Design:
- Patients will be stratified into four cohorts according to their hepatic function.
- Pazopanib will be administered orally once daily on days 1-21 of a 21-day cycle.
- Blood samples for PK will be collected from all patients.
- A minimum of 2 and a maximum of 12 patients will be accrued in each liver dysfunction group at each dose, with 12 patients entered at the recommended dose level in each group. At least 12 patients will be accrued in the normal liver function group. The estimated maximum accrual is 132 patients, including all centers.
- Being tested
- Pazopanib, Pazopanib (GW786034)(GW786034)
- Keywords
- Pazopanib, Tyrosine Kinase Inhibitor, Advanced Cancer, Pharmacokinetics, Cancer, Solid Tumor, Lymphoma
- Medical subject headings
- Neoplasms, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Pazopanib (GW786034)(GW786034)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the MTD and DLT of pazopanib in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) to provide appropriate dosing recommendations for panzopanib in such patients.
Secondary outcomes (1)
To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of pazopanib and metabolites (GSK1071306, GSK1268992, GSK1268997, and GW700201) in patients with varying degrees of hepatic dysfunction.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2008 (estimated)
- Study start7 Oct 2008
- Primary completion22 Jan 2013
- Study completion22 Jan 2013
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 NeoplasmsStudies 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Shivaani Kummar, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00674024
- Sponsor's protocol ID
- 090003
- Other IDs
- 09-C-0003
- Status last verified
- 22 Jan 2013
- First submitted
- 6 May 2008
- Last updated
- 20 Nov 2019
- Results posted
- No
Publications
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
PubMed 17242396Conn HO. A peek at the Child-Turcotte classification. Hepatology. 1981 Nov-Dec;1(6):673-6. doi: 10.1002/hep.1840010617. No abstract available.
PubMed 7308998Conn HO, Resnick RH, Grace ND, Atterbury CE, Horst D, Groszmann RJ, Gazmuri P, Gusberg RJ, Thayer B, Berk D, Wright SC, Vollman R, Tilson DM, McDermott WV, Cohen JA, Kerstein M, Toole AL, Maselli JP, Razvi S, Ishihara A, Stern H, Trey C, O'Hara ET, Widrich W, Aisenberg H, Stansel HC, Zinny M. Distal splenorenal shunt vs. portal-systemic shunt: current status of a controlled trial. Hepatology. 1981 Mar-Apr;1(2):151-60. doi: 10.1002/hep.1840010211.
PubMed 7026401
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I and Pharmacokinetic Single Agent Study of Pazopanib in Adults With Advanced Malignancies and Varying Degrees of Liver Dysfunction
- ClinicalTrials.gov ID
- NCT00674024
- Acronym / sponsor ID
- 090003
- Keywords
- Pazopanib, Tyrosine Kinase Inhibitor, Advanced Cancer, Pharmacokinetics, Cancer, Solid Tumor, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 7 Oct 2008
- Primary completion
- 22 Jan 2013 (actual)
- Study completion
- 22 Jan 2013 (actual)
- First posted
- 7 May 2008 (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.
Background:
- Pazopanib is an experimental drug that was designed to enter cancer cells and block the activity of proteins that are important for cancer cell growth and survival.
- This is the first study in which pazopanib is given to patients with different degrees of liver function. The safe dose for patients with normal liver function is already known.
Objectives:
- To determine the safety and side effects of pazopanib given at different dose levels to patients with cancer who have different degrees of liver function.
- To find out how much pazopanib is in the blood at specific times.
- To determine if pazopanib is effective in treating advanced cancer in patients with different degrees of liver function.
Eligibility:
- Patients 18 years of age and older with an advanced solid tumor or lymphoma that cannot be treated successfully with standard therapies and who have normal or abnormal liver function.
Design:
- Treatment:
- Patients are divided into 4 groups, based on their liver function. The first three patients in each group receive a low dose of pazopanib. The next three in each group receive a higher dose of pazopanib if no serious side effects were reported in the previous three. The dose is increased in succeeding groups of three patients until the maximum study dose is reached.
- Patients take pazopanib once a day by mouth in 21-day treatment cycles. Treatment continues until the cancer worsens, the patient develops severe side effects, the patient no longer wants to continue the study, or the doctor removes the patient from the study for other reasons.
- Monitoring:
- Blood pressure: Patients monitor and record their blood pressure twice a day after starting treatment.
- Blood tests: Patients have weekly routine blood tests. In addition, at week 3 of the first cycle and again after the highest safe dose has been determined, several blood samples are collected at frequent intervals to determine how the body handles the drug.
- Imaging studies: X-rays or scans or both are done to measure the extent of disease every 3 cycles.
- Physical examinations are done at periodic intervals.
Detailed description
Background:
- Pazopanib is a potent, multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alpha, PDGFR-beta, and c-kit with the potential to inhibit angiogenesis, lymphangiogenesis, and tumor growth that may have an advantage over agents with a narrower kinase specificity profile.
- Pazopanib has shown activity in renal cell cancer with tumor shrinkage and stable disease; Phase I, II, and III trials as single therapy and in combination with lapatinib are ongoing or planned in patients with various solid tumors.
- Pazopanib appears to be well tolerated at doses from 50 mg three times weekly to 2000 mg daily; the most common adverse events are hypertension, diarrhea, nausea, fatigue, and hair depigmentation.
Objectives:
- To establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of pazopanib in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) in order to provide appropriate dosing recommendations for pazopanib in such patients.
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of pazopanib and metabolites (GSK1071306, GSK1268992, GSK1268997, and GW700201) in patients with varying degrees of hepatic dysfunction.
- To document the non-DLTs associated with administration of pazopanib in patients with hepatic dysfunction.
- To explore correlations of the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma PK, and PD of pazopanib administration.
- To document any antitumor activity associated with pazopanib treatment of patients enrolled on this study.
Eligibility:
- Adult patients must have histologically or cytologically confirmed solid tumor or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must have adequate renal and bone marrow function.
Study Design:
- Patients will be stratified into four cohorts according to their hepatic function.
- Pazopanib will be administered orally once daily on days 1-21 of a 21-day cycle.
- Blood samples for PK will be collected from all patients.
- A minimum of 2 and a maximum of 12 patients will be accrued in each liver dysfunction group at each dose, with 12 patients entered at the recommended dose level in each group. At least 12 patients will be accrued in the normal liver function group. The estimated maximum accrual is 132 patients, including all centers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- For patients at the NCI, histological or cytological confirmation of solid tumor or lymphoma diagnosis will be performed at the NCI Laboratory of Pathology.
Key exclusion criteria (2 listed)
- Patients who have had prior treatment with pazopanib will not be eligible for this study.
- Patients with abnormal liver function except grade 4 AST, grade 4 ALT, and grade 4 bilirubin will be eligible and will be grouped according to the criteria in Section 5.1. For assessing hepatic dysfunction, greater than 35 percent of the total bilirubin must be direct bilirubin.
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 |
|---|---|---|
| Pazopanib | Drug | – |
| Pazopanib (GW786034)(GW786034) | Drug | – |
Primary outcome
To establish the MTD and DLT of pazopanib in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) to provide appropriate dosing recommendations for panzopanib in such patients.
1 secondary outcome
To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of pazopanib and metabolites (GSK1071306, GSK1268992, GSK1268997, and GW700201) in patients with varying degrees of hepatic dysfunction.
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 20 Nov 2019.
- Background: PubMed 17242396Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
- Background: PubMed 7308998Conn HO. A peek at the Child-Turcotte classification. Hepatology. 1981 Nov-Dec;1(6):673-6. doi: 10.1002/hep.1840010617. No abstract available.
- Background: PubMed 7026401Conn HO, Resnick RH, Grace ND, Atterbury CE, Horst D, Groszmann RJ, Gazmuri P, Gusberg RJ, Thayer B, Berk D, Wright SC, Vollman R, Tilson DM, McDermott WV, Cohen JA, Kerstein M, Toole AL, Maselli JP, Razvi S, Ishihara A, Stern H, Trey C, O'Hara ET, Widrich W, Aisenberg H, Stansel HC, Zinny M. Distal splenorenal shunt vs. portal-systemic shunt: current status of a controlled trial. Hepatology. 1981 Mar-Apr;1(2):151-60. doi: 10.1002/hep.1840010211.
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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.
Shivaani Kummar, M.D. principal investigator
National Cancer Institute (NCI)
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 Pazopanib and Pazopanib (GW786034)(GW786034) in people with Neoplasms and Lymphoma, 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.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2019. 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.
What does the primary outcome measure?
To establish the MTD and DLT of pazopanib in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) to provide appropriate dosing recommendations for panzopanib in such patients.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00674024, 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 20 Nov 2019.