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

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04635111
• Collaborator: (none)
• Enrollment: 30
• Locations: 5
• Anticipated Duration (Months): 181.7
• Patients Per Site: 6
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatotoxicity; Tenosynovial Giant Cell Tumor	Drug: TURALIO™

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 Design

• Study Type: Observational [Patient Registry]
• Anticipated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Long-term Study to Further Evaluate the Risk of Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment
• Actual Study Start Date: Jan 7, 2021
• Anticipated Primary Completion Date: Jun 1, 2025
• Anticipated Study Completion Date: Mar 1, 2036

Arms and Interventions

Arm	Intervention/Treatment
Symptomatic TGCT Participants 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).	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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Number of Participants With A Liver Transplant [Baseline up to 10 years]

3. Number of Participants Experiencing Death [Baseline up to 10 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Hematology and Oncology	Santa Monica	California	United States	90404
2	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90602-3171
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Montefiore Medical Center	New York	New York	United States	10467
5	OSU - James Comprehensive Cancer Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT04635111
• Other Study ID Numbers: PL3397-A-U401
• First Posted: Nov 18, 2020
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Daiichi Sankyo, Inc.: Hepatotoxicity; Tenosynovial Giant Cell Tumor; Pexidartinib; TURALIO™
• Additional relevant MeSH terms: Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath

Study Results

No Results Posted as of Aug 23, 2022