A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

Tenosynovial Giant Cell Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04703322
• Other study ID #: PL3397-A-J304
• Secondary ID: jRCT2041200074
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2021
• Est. completion date: November 30, 2026

Study information

• Verified date: July 2023
• Source: Daiichi Sankyo, Inc.
• Contact: Daiichi Sankyo Contact for Clinical Trial Information
• Phone: +81-3-6225-1111(M-F 9-5 JST)
• Email: dsclinicaltrial[@]daiichisankyo.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: November 30, 2026
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Tenosynovial Giant Cell Tumor

Intervention

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

Locations

Country	Name	City	State
Japan	Nagoya University Hospital	Aichi
Japan	Kyushu University Hospital	Fukuoka
Japan	Kanazawa University Hospital	Ishikawa
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	National Cancer Center Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting Toxicity (DLT) in Part 1	The number of participants with dose-limiting toxicities will be assessed.	Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)
Primary	Analysis of Pharmacokinetic Parameter: Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1	Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.	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)
Primary	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	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.	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)
Primary	Analysis of Pharmacokinetic Parameter: Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1	AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.	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)
Primary	Analysis of Pharmacokinetic Parameter: Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1	Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.	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)
Primary	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.	Week 25
Secondary	ORR Based on Tumor Volume Score (TVS) in Part 2	ORR will be assessed by centrally reviewed MRI scan based on TVS.	Week 25
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 3 years 6 months