Pazopanib to Treat Adults With Advanced Cancers and Varying Degrees of Liver Function
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Brain Cancer, Lymphoma, Gastrointestinal, Hematology |
| Therapuetic Areas: | Gastroenterology, Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - 110 |
| Updated: | 2/6/2019 |
| Start Date: | October 7, 2008 |
| End Date: | January 22, 2013 |
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.
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.
- 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.
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.
- 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.
- INCLUSION CRITERIA:
For patients at the NCI, histological or cytological confirmation of solid tumor or
lymphoma diagnosis will be performed at the NCI Laboratory of Pathology.
EXCLUSION CRITERIA:
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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