Pazopanib to Treat Adults With Advanced Cancers and Varying Degrees of Liver Function

November 19, 2019 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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.

Secondary Outcome Measures

Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Shivaani Kummar, M.D., National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 7, 2008

Primary Completion (Actual)

January 22, 2013

Study Completion (Actual)

January 22, 2013

Study Registration Dates

First Submitted

May 6, 2008

First Submitted That Met QC Criteria

May 6, 2008

First Posted (Estimate)

May 7, 2008

Study Record Updates

Last Update Posted (Actual)

November 20, 2019

Last Update Submitted That Met QC Criteria

November 19, 2019

Last Verified

January 22, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 090003
  • 09-C-0003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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