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A Phase I and Pharmacokinetic Single Agent Study of Pazopanib in Adults With Advanced Malignancies and Varying Degrees of Liver Dysfunction


Phase 1
18 Years
N/A
Not Enrolling
Both
Neoplasms, Lymphoma

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Trial Information

A Phase I and Pharmacokinetic Single Agent Study of Pazopanib in Adults With Advanced Malignancies and Varying Degrees of Liver Dysfunction


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.

Inclusion Criteria


- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Principal Investigator

Luigi Ferrucci, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute on Aging (NIA)

Authority:

United States: Federal Government

Study ID:

090003

NCT ID:

NCT00674024

Start Date:

October 2008

Completion Date:

January 2013

Related Keywords:

  • Neoplasms
  • Lymphoma
  • Pazopanib
  • Tyrosine Kinase Inhibitor
  • Advanced Cancer
  • Pharmacokinetics
  • Cancer
  • Solid Tumor
  • Lymphoma
  • Neoplasms
  • Lymphoma

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892
City of Hope National Medical CenterLos Angeles, California  91010