Clinical trial NCT04703322: A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan
Official title: A Phase 2, Multicenter, Two-Part, Open-Label Study of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor in Japan
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Tenosynovial Giant Cell Tumor
Keywords: Tenosynovial Giant Cell Tumor
TGCT
Giant Cell Tumor of Tendon Sheath
GCTTS
Pigmented Villonodular Synovitis
PVNS
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2021-01-11
Enrollment: 9
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Dose-limiting Toxicity (DLT) in Part 1
timeFrame: Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)
measure: Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1
timeFrame: 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)
measure: Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1
timeFrame: 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)
measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2
timeFrame: Week 25
Secondary outcomes:
measure: ORR Based on Tumor Volume Score (TVS) in Part 2
timeFrame: Week 25
measure: Range of Motion (ROM) in Part 2
timeFrame: Week 25
measure: Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2
timeFrame: Week 25
measure: Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2
timeFrame: Week 25
measure: Best Overall Response (BOR) Based on RECIST Version 1.1 in Part 2
timeFrame: Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
measure: BOR Based on TVS in Part 2
timeFrame: Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
measure: Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2
timeFrame: Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
measure: DoR Based on TVS
timeFrame: Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months
measure: Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events
timeFrame: Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Nagoya University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Ishikawa
country: Japan
facility: Kanazawa University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: