A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

A Phase 2, Multicenter, Two-Part, Open-Label Study of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor in Japan

This phase 2, multicenter, two-part, open-label, single-arm study will be conducted in Japan and will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of pexidartinib in adult participants with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitation and not amenable to improvement with surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Tenosynovial Giant Cell Tumor
• Intervention / Treatment: Drug: Pexidartinib

Detailed Description

This study will consist of 2 parts. In Part 1, pexidartinib 800 mg/day (400 mg twice a day [BID]) will be administered on an empty stomach and tolerability and PK of pexidartinib will be evaluated to determine the initiation of Part 2. In Part 2, pexidartinib 800 mg/day (400 mg BID) will be administered on an empty stomach and efficacy, safety, and PK of pexidartinib will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥20 years
• A diagnosis of TGCT (i) that has been histologically confirmed by a pathologist1 and (ii) associated with severe morbidity or functional limitations and not amenable to improvement with surgery determined consensually by qualified personnel (eg, 2 surgeons or a multi-disciplinary tumor board).
• Measurable disease as defined by RECIST version 1.1 (except that a minimal size of 2 cm is required), assessed from MRI scan by a central radiologist.

Exclusion Criteria:

• Known metastatic TGCT.
• Pre-existing increased serum transaminases; total bilirubin or direct bilirubin (>upper limit of normal); or active liver or biliary tract disease, including increased alkaline phosphatase.
• Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator's opinion, would likely interfere with a participant's study participation or the interpretation of his or her results.
• Use of strong cytochrome P450 3A inducers, including St John's wort, proton pump inhibitors and potassium-competitive acid blockers, or other products known to cause hepatotoxicity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pexidartinib; Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]).	Drug: Pexidartinib; 400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration); Other Names: PLX3397; TURALIO™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicity (DLT) in Part 1	The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed.	Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)
Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1	Pharmacokinetic parameters were assessed using non-compartmental methods. Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.	Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days)
Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of Pexidartinib and ZAAD-1006a (AUClast) in Part 1	Pharmacokinetic parameters were assessed using non-compartmental methods. AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of pexidartinib and ZAAD-1006a in plasma.	Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days)
Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1	Pharmacokinetic parameters were assessed using non-compartmental methods. AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.	Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days)
Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1	Pharmacokinetic parameters were assessed using non-compartmental methods. Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.	Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days)
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2	ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.	Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR Based on Tumor Volume Score (TVS) in Part 2	ORR will be assessed by centrally reviewed MRI scan based on TVS.	Week 25
Range of Motion (ROM) in Part 2	Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed.	Week 25
Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2	Mean change from baseline score in the PROMIS Physical Function Scale will be assessed.	Week 25
Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2	Proportion of responders will be assessed based on the BPI Worst Pain NRS item and analgesic use by BPI-30 definition (ie, 30% or more improvement in average NRS).	Week 25
BOR Based on TVS in Part 2	BOR will be assessed by centrally reviewed MRI scan based on TVS.	Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2	DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.	Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
DoR Based on TVS	DoR will be assessed by centrally reviewed MRI scan based on TVS.	Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
Best Overall Response (BOR) Based on RECIST Version 1.1 in Part 2	BOR will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1.	Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events		Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Actual): March 20, 2023
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: January 8, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Tenosynovial Giant Cell Tumor; TGCT; PVNS; Pigmented Villonodular Synovitis; Giant Cell Tumor of Tendon Sheath; GCTTS
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Joint Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Synovitis; Tendinopathy; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular; pexidartinib
• Other Study ID Numbers: PL3397-A-J304; jRCT2041200074 (Other Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: Yes