Hepatic Monitoring for Pazopanib

NCT01449825 | Completed

• 2 other identifiers: 114430WEUKSTV4601
• Study Type: observational
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Carcinoma, Renal Cell

Keywords

hepatic safety; prescriber compliance; pazopanib; epidemiology

Outcome Measures

Primary Outcomes (3)

• Prescriber compliance with pazopanib label guidelines for liver monitoring

  Prescriber compliance with pazopanib label guidelines for liver monitoring

  Over four years of treatment with pazopanib

• Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law

  Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law

  Over four years of treatment with pazopanib

• Incidence of acute liver failure (ALF)

  Incidence of ALF

  Over four years of treatment with pazopanib

Study Arms (4)

Prescriber compliance group

Adult (18+ years) new users of pazopanib with an indication of RCC evaluated for prescriber compliance

Drug: Pazopanib use

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; Drug: Use of sunitinib, bevacizumab, or 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; Drug: Use of sunitinib, bevacizumab, or 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; Drug: Use of sunitinib, bevacizumab, or sorafenib

Interventions

Pazopanib use DRUG

Treatment with pazopanib

Incidence of cases of ALF group; Incidence of drug induced liver injury (DILI) cases group; Incidence of liver chemistry test (LCT) elevation group; Prescriber compliance group

Use of sunitinib, bevacizumab, or sorafenib DRUG

Treatment with any of the three other marketed anti-VEGF drugs: sunitinib, bevacizumab, and sorafenib

Incidence of cases of ALF group; Incidence of drug induced liver injury (DILI) cases group; Incidence of liver chemistry test (LCT) elevation group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• N/A

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Bevacizumab; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 10, 2011
• Study Start: December 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 21, 2014

Record last verified: 2014-04