A Long-term Study Evaluating Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment

Recruiting

• Conditions: Tenosynovial Giant Cell Tumor; Hepatotoxicity
• Interventions: Drug: TURALIO™

• Registration Number: NCT04635111
• Lead Sponsor: Daiichi Sankyo

Brief Summary

A study to evaluate the long-term risk of hepatic failure with TURALIO™ (pexidartinib) and the mechanism of liver injury based upon liver biopsy information among patients who received or are receiving TURALIO™ (pexidartinib) and experience hepatotoxicity.

Detailed Description

This FDA post-marketing requirement study will evaluate the long-term risk of hepatic failure with TURALIO™ (pexidartinib) and the mechanism of liver injury based upon liver biopsy information among patients who received or are receiving TURALIO™ (pexidartinib) for symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery, and who experience hepatotoxicity. A liver biopsy will be collected from enrolled patients for central laboratory analysis of macrophage and immune cell profiles to investigate possible mechanisms of the hepatotoxicity. Additionally, 4 blood samples will be collected to evaluate liver function, other relevant safety tests, peripheral immune cells, and for pharmacogenomic testing. Enrolled patients will be followed at least yearly for 10 years to assess long-term risk of hepatic failure.

Study Timeline

• Study First Submitted: 2020-10-29
• Study First Submitted QC: 2020-11-17
• Study First Posted: 2020-11-18
• Study Start: 2021-01-07
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-02
• Primary Completion: 2025-06-01
• Study Completion: 2036-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Adult participants with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery

• Age ≥18 years old

• Emergence of at least one of the following liver test abnormalities due to TURALIO™ (pexidartinib) exposure:

  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) >2 × ULN
  • Isolated TBIL >2 × ULN (excluding patients with Gilbert's syndrome)
  • Isolated AST or ALT >10 × ULN
  • Alkaline phosphatase (ALP) >2 x ULN with gamma-glutamyl transferase (GGT) >2 x ULN

• Consent to study procedures, long-term safety follow-up, and use of data from the TURALIO™ (pexidartinib) Risk Evaluation and Mitigation Strategy (REMS) program

Exclusion Criteria

• Not applicable

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Symptomatic TGCT Participants	TURALIO™	Adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery, and who experience moderate or severe hepatotoxicity due to use of TURALIO™ (pexidartinib).

Primary Outcome Measures

Name	Time	Method
Frequency of Hepatic Failure After Discontinuation of TURALIO™ (pexidartinib)	Baseline up to 10 years	Hepatic failure is defined as severe liver injury with encephalopathy and impaired synthetic function (INR \>= 1.5) as well as liver transplant and hepatic-related death.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Liver Test Abnormalities	Baseline up to 10 years	Liver test abnormalities were defined as the following: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) \>2 × ULN; Isolated TBIL \>2 × ULN (excluding patients with Gilbert's syndrome); Isolated AST or ALT \>10 × ULN; Alkaline phosphatase (ALP) \>2 x ULN with gamma-glutamyl transferase (GGT) \>2 x ULN.
Number of Participants With A Liver Transplant	Baseline up to 10 years
Number of Participants Experiencing Death	Baseline up to 10 years

Trial Locations

Locations (8)

Kelsey Seybold Clinic - Pearland; 🇺🇸 Houston, Texas, United States

Kamalesh K Sankhala MD INC; 🇺🇸 Santa Monica, California, United States

OSU - James Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Sarcoma Oncology Research Center LLC; 🇺🇸 Santa Monica, California, United States

UCLA Hematology and Oncology; 🇺🇸 Santa Monica, California, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

The Oncology Institute of Hope and Innovation; 🇺🇸 Whittier, California, United States

Montefiore Medical Center; 🇺🇸 New York, New York, United States