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

Tenosynovial Giant Cell Tumor Clinical Trial

Official title:

A Long-term Study to Further Evaluate the Risk of Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04635111
• Other study ID #: PL3397-A-U401
• Status: Recruiting
• Start date: January 7, 2021
• Est. completion date: March 2036

Study information

• Verified date: September 2023
• Source: Daiichi Sankyo, Inc.
• Contact: Daiichi Sankyo Contact for Clinical Trial Information
• Phone: 908-992-6400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2036
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Hepatotoxicity
• Tenosynovial Giant Cell Tumor

Intervention

Drug:
• TURALIO™
This is a non-interventional, observational study to evaluate long-term risk of hepatic failure associated with TURALIO™ (pexidartinib) treatment. No study medication will be provided to the participants.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	OSU - James Comprehensive Cancer Center	Columbus	Ohio
United States	Montefiore Medical Center	New York	New York
United States	Kamalesh K Sankhala MD INC	Santa Monica	California
United States	UCLA Hematology and Oncology	Santa Monica	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Hepatic Failure After Discontinuation of TURALIO™ (pexidartinib)	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.	Baseline up to 10 years
Secondary	Number of Participants With Liver Test Abnormalities	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.	Baseline up to 10 years
Secondary	Number of Participants With A Liver Transplant		Baseline up to 10 years
Secondary	Number of Participants Experiencing Death		Baseline up to 10 years