A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

Phase 2Active Not RecruitingNCT04703322

Daiichi Sankyo Co., Ltd.9 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Tenosynovial Giant Cell Tumor

Interventions

PexidartinibDRUG

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

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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.

Locations (6)

Nagoya University Hospital

Aichi, Japan

Kyushu University Hospital

Fukuoka, Japan

Kanazawa University Hospital

Ishikawa, Japan

National Hospital Organization Osaka National Hospital

Osaka, Japan

Outcomes

Primary Outcomes

Dose-limiting Toxicity (DLT) in Part 1

The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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

ORR will be assessed by centrally reviewed MRI scan based on TVS.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: Week 25

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.

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

BOR Based on TVS in Part 2

BOR will be assessed by centrally reviewed MRI scan based on TVS.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months