Neoplasms

All Conditions

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Wounds and Injuries

Nervous System Diseases

Rare Diseases

Giant Cell Tumors

Giant Cell Tumor of Tendon Sheath

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Synovitis

Joint Diseases

Tendinopathy

Muscular Diseases

Pigmented Villonodular Synovitis

400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)

Pexidartinib

Global Clinical Leader

This study will assess pexidartinib in adult participants with symptomatic TGCT that is associated with severe morbidity or functional limitations and not amendable to improvement with surgery.

Participants with symptomatic TGCT will be administered pexidartinib 400 mg twice daily continuously with 28-day treatment cycle until criteria for discontinuation are reached. Participants who complete primary endpoint assessments may be eligible to continue receiving pexidartinib until disease progression, unacceptable toxicity, the occurrence of other termination criteria, or withdrawal from the study. Eligible participants' status will be collected every 6 months as a long term follow-up at least 2 years.

A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT

Multicenter, Single Arm Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by centrally reviewed MRI scan. Complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; and overall response rate (ORR), defined as CR+PR, are presented.

For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Tumor Volume Score (TVS) by centrally reviewed MRI scan. Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. Complete response (CR), disappearance of lesion; partial response (PR), at least 50% decrease in volume score relative to baseline; overall response rate (ORR), defined as CR+PR, are presented.

Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. The relative ROM was calculated (expressed in percent) as follows: Relative ROM = 100 x (absolute ROM measured)/(reference ROM standard). The change from baseline in relative ROM at Week 25 was calculated as the difference in relative ROM at Week 25 visit minus relative ROM at Screening visit.

The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess the physical function of the upper and lower limbs. The scale ranges from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.

Best overall response (CR or PR) of pexidartinib based on RECIST 1.1 and TVS are summarized. Tumor categories for RECIST v1.1 were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions; stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions; and not evaluable (NE). Tumor categories for TVS were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 50% decrease in volume score relative to baseline; stable disease (SD), does not meet any of the prior criteria based on score during study; progressive disease (PD), at least a 30% increase in in volume relative to lowest score during the study whether at baseline or some other visit; and not evaluable (NE).

Duration of response (DOR) is defined as the date of the first recorded response to the first date of documented disease progression.

A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until post-treatment visit (28 ± 7 days after the last dose of study drug).

AUC(0-6h) was calculated using standard non-compartmental analysis. AUC(0-6h) for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.

Cmax was calculated using standard non-compartmental analysis. Cmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.

Tmax was calculated using standard non-compartmental analysis. Tmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.

Daiichi Sankyo Co., Ltd.

Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

China

Taiwan

Region of Enrollment

Baseline characteristics were assessed in the Safety Analysis Set.

Clinical Director

ORR based on RECIST 1.1 was assessed in the Full Analysis Set.

Overall Response Rate (ORR) of Pexidartinib Based on RECIST 1.1 of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25

ORR based on TVS was assessed in the Full Analysis Set.

Overall Response Rate (ORR) of Pexidartinib Based on TVS of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25

Mean Percent Change From Baseline for Range of Motion (ROM) was assessed in Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.

Mean Percent Change From Baseline for Range of Motion (ROM) Score in Participants Receiving Pexidartinib

Mean Change From PROMIS was assessed in the Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.

Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib

Best Overall Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan

Duration of Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan

Number of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term

ZAAD-1006a

AUC(0-6h) was assessed in the Pharmacokinetic Analysis Set.

Area Under the Plasma Concentration Time Curve From Time 0 to 6 Hours AUC(0-6h) in Participants Receiving Pexidartinib

Cmax was assessed in the Pharmacokinetic Analysis Set.

Maximum Plasma Concentration (Cmax) in Participants Receiving Pexidartinib

Tmax was assessed in the Pharmacokinetic Analysis Set.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Participants Receiving Pexidartinib

Overall Study

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).

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.

TURALIO™

Daiichi Sankyo Contact for Clinical Trial Information

Principal Investigator

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.

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.

The liver biopsy will be performed as soon as reasonably possible after the liver test abnormality criteria are first met and before liver tests have returned to normal. Four blood samples will be drawn on the day of, or up to 4 days before, the biopsy. One sample will evaluate liver test results (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase \[ALP\], gammaglutamyl transferase \[GGT\], total bilirubin \[TBIL\], direct bilirubin), serum creatinine, and blood urea nitrogen (BUN) at the study site. The remaining three samples will be used for central laboratory analysis.

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

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

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT	NCT04488822	Tenosynovial Gi...	Pexidartinib	18 Years -	Daiichi Sankyo
A Long-term Study Evaluating Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment	NCT04635111	Hepatotoxicity Tenosynovial Gi...	TURALIO™	18 Years -	Daiichi Sankyo
A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT	NCT04488822	Tenosynovial Gi...	Pexidartinib	18 Years -	Daiichi Sankyo
A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT	NCT04488822	Tenosynovial Gi...	Pexidartinib	18 Years -	Daiichi Sankyo

Spots Global Cancer Trial Database for turalio™

Every month we try and update this database with for turalio™ cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for turalio™

Every month we try and update this database with for turalio™ cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for turalio™ cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.