A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

NCT04703322 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: PL3397-A-J304jRCT2041200074
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Tenosynovial Giant Cell Tumor

Keywords

Tenosynovial Giant Cell Tumor; TGCT; Giant Cell Tumor of Tendon Sheath; GCTTS; Pigmented Villonodular Synovitis; PVNS

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (9)

• ORR Based on Tumor Volume Score (TVS) in Part 2

  Week 25

• Range of Motion (ROM) in Part 2

  Week 25

• Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2

  Week 25

• Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2

  Week 25

• Best Overall Response (BOR) Based on RECIST Version 1.1 in Part 2

  Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months

Study Arms (1)

Pexidartinib

EXPERIMENTAL

Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily \[BID\]).

Drug: Pexidartinib

Interventions

Pexidartinib DRUG

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

Also known as: TURALIO™, PLX3397

Pexidartinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead

Study Sites (6)

Nagoya University Hospital

Aichi, 466-8560, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Kanazawa University Hospital

Ishikawa, 920-8641, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, 540-0006, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

MeSH Terms

Conditions

Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular

Interventions

pexidartinib

Condition Hierarchy (Ancestors)

Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Synovitis; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: January 11, 2021
• Study Start: March 15, 2021
• Primary Completion: March 20, 2023
• Study Completion (Estimated): May 31, 2026
• Last Updated: March 4, 2026
• Results First Posted: March 3, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

JP (6)