Optic

ID

Name

PL3397-A-J304

Description

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.

Trial arms

Trial start

2021-03-15

Estimated PCD

2025-02-28

Trial end

2026-11-30

Status

Recruiting

Phase

Early phase I

Treatment

Pexidartinib

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

Arms:

Pexidartinib

Other names:

TURALIO™, PLX3397

Size

21

Primary endpoint

Dose-limiting Toxicity (DLT) in Part 1

Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)

Analysis of Pharmacokinetic Parameter: Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1

Cycle 1, Day 1 to Cycle 1, Day 2 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours postdose; Cycle 1, Day 15 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours (each cycle is 28 days)

Analysis of 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

Cycle 1, Day 1 to Cycle 1, Day 2 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours postdose; Cycle 1, Day 15 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours (each cycle is 28 days)

Analysis of Pharmacokinetic Parameter: Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1

Cycle 1, Day 1 to Cycle 1, Day 2 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours postdose; Cycle 1, Day 15 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours (each cycle is 28 days)

Analysis of Pharmacokinetic Parameter: Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1

Cycle 1, Day 1 to Cycle 1, Day 2 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours postdose; Cycle 1, Day 15 predose, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours (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

Week 25

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 21, 'type': 'ESTIMATED'}}

Updated at

2023-07-12

Product

Pexidartinib

Indication

Tenosynovial Giant Cell Tumor

Organization

Daiichi Sankyo

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