Hepatic Monitoring for Pazopanib

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01449825
First received: October 6, 2011
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

Pazopanib is approved by the FDA and EMA as targeted therapy for the indication of advanced renal cell carcinoma (RCC). Hepatic safety events were observed in the pazopanib pivotal clinical trial and the U.S. pazopanib label information contains a 'black box warning' regarding hepatotoxicity. These clinical observations have prompted GSK to undertake a proactive pharmacovigilance strategy focused on hepatic safety that goes beyond spontaneous reporting of adverse events.

The goals of the study are to assess prescriber compliance with pazopanib label guidelines for liver monitoring among patients with RCC, as well as to quantify and characterize the hepatic safety profile of the product in real-world clinical practice compared to other anti-vascular endothelial growth factor (anti-VEGF) drugs. As part of regulatory commitments, GSK will conduct parallel epidemiologic analyses in different patient populations as represented in multiple databases of electronic medical records. To enhance accrual of data, GSK will conduct this safety surveillance program simultaneously across datasets in order to detect and characterize all cases of liver enzyme elevations in diverse populations of patients receiving pazopanib. Two additional goals of this study are to evaluate the incidence of cases of combinations of liver enzyme elevations indicative of Hy's Law and drug-induced acute liver failure among users of pazopanib compared to users of other anti-VEGF drugs. This research effort will be coordinated by an external coordinating center.

An epidemiologic cohort study design, nested in several databases of electronic medical information, will be employed for the research questions. Following the availability of pazopanib in the relevant medical care system, the study will collect retrospective data at regular intervals over the course of four years among persons exposed to pazopanib and other anti-VEGF agents. Each patient will be characterized based on additional available information in the database (e.g., demographics, concomitant medications). Elevations in liver enzymes will be identified through laboratory data captured in these databases. Potential Hy's Law and acute liver failure cases will be identified through established screening criteria, and screen-positive cases will be reviewed by an adjudication committee of hepatologists for final determination of drug-associated causality.


Condition Intervention
Carcinoma, Renal Cell
Drug: Pazopanib use
Drug: Use of sunitinib, bevacizumab, or sorafenib

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Postmarketing Hepatic Monitoring for Pazopanib Using Observational Databases

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Prescriber compliance with pazopanib label guidelines for liver monitoring [ Time Frame: Over four years of treatment with pazopanib ] [ Designated as safety issue: Yes ]
    Prescriber compliance with pazopanib label guidelines for liver monitoring

  • Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law [ Time Frame: Over four years of treatment with pazopanib ] [ Designated as safety issue: Yes ]
    Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law

  • Incidence of acute liver failure (ALF) [ Time Frame: Over four years of treatment with pazopanib ] [ Designated as safety issue: Yes ]
    Incidence of ALF


Enrollment: 1
Study Start Date: December 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Prescriber compliance group
Adult (18+ years) new users of pazopanib with an indication of RCC evaluated for prescriber compliance
Drug: Pazopanib use
Treatment with pazopanib
Incidence of liver chemistry test (LCT) elevation group
Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib in monotherapy who have a baseline LCT evaluated for LCT elevations
Drug: Pazopanib use
Treatment with pazopanib
Drug: Use of sunitinib, bevacizumab, or sorafenib
Treatment with any of the three other marketed anti-VEGF drugs: sunitinib, bevacizumab, and sorafenib
Incidence of drug induced liver injury (DILI) cases group
Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) longitudinally followed up in order to capture occurrences of LCT elevations consistent with Hy's Law to evaluate for drug-induced liver injury
Drug: Pazopanib use
Treatment with pazopanib
Drug: Use of sunitinib, bevacizumab, or sorafenib
Treatment with any of the three other marketed anti-VEGF drugs: sunitinib, bevacizumab, and sorafenib
Incidence of cases of ALF group
Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) longitudinally followed up in order to capture occurrences of ICD-9 codes indicative of possible ALF to evaluate for drug-induced liver injury
Drug: Pazopanib use
Treatment with pazopanib
Drug: Use of sunitinib, bevacizumab, or sorafenib
Treatment with any of the three other marketed anti-VEGF drugs: sunitinib, bevacizumab, and sorafenib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The study population consists of adult (18+years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib.

Two U.S. healthcare databases and one Dutch-linked medical registry system will contribute de-identified and anonymised data from electronic medical records to the surveillance program.

Criteria

Inclusion Criteria:

  • In the prescriber compliance analysis, all adult (18+ years) new users of pazopanib with an indication of RCC will be eligible for the analysis.
  • In the liver enzyme elevation analysis, all adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib in monotherapy for any cancer type who have a baseline liver enzyme value will be eligible for the analysis.
  • In the drug-induced liver injury analyses, all adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) will be longitudinally followed up in order to capture occurrences of liver enzyme elevations consistent with Hy's Law and ICD-9 codes indicative of possible ALF to evaluate for drug-induced liver injury.

Exclusion Criteria:

  • N/A
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01449825

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01449825     History of Changes
Other Study ID Numbers: 114430, WEUKSTV4601
Study First Received: October 6, 2011
Last Updated: April 17, 2014
Health Authority: United States: No Health Authority

Keywords provided by GlaxoSmithKline:
hepatic safety
prescriber compliance
pazopanib
epidemiology

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Sunitinib
Sorafenib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014