Clinical trial NCT04635111: A Long-term Study Evaluating Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment
Official title: A Long-term Study to Further Evaluate the Risk of Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatotoxicity
Tenosynovial Giant Cell Tumor
Keywords: Hepatotoxicity
Tenosynovial Giant Cell Tumor
Pexidartinib
TURALIO™
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2020-11-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery, who experience moderate or severe hepatotoxicity due to TURALIO™ (pexidartinib).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of Hepatic Failure After Discontinuation of TURALIO™ (pexidartinib)
timeFrame: Baseline up to 10 years
Secondary outcomes:
measure: Number of Participants With Liver Test Abnormalities
timeFrame: Baseline up to 10 years
measure: Number of Participants With A Liver Transplant
timeFrame: Baseline up to 10 years
measure: Number of Participants Experiencing Death
timeFrame: Baseline up to 10 years
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Kamalesh K Sankhala MD INC
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center LLC
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology and Oncology
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Columbus
country: United States
facility: OSU - James Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: Kelsey Seybold Clinic - Pearland
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: