A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pexidartinib Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]). |
Drug: Pexidartinib
400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose-limiting Toxicity (DLT) in Part 1 [Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)]
The number of participants with dose-limiting toxicities will be assessed.
- 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)]
Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.
- 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)]
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.
- 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)]
AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.
- 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)]
Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.
- Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2 [Week 25]
ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.
Secondary Outcome Measures
- ORR Based on Tumor Volume Score (TVS) in Part 2 [Week 25]
ORR will be assessed by centrally reviewed MRI scan based on TVS.
- Range of Motion (ROM) in Part 2 [Week 25]
Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed.
- Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2 [Week 25]
Mean change from baseline score in the PROMIS Physical Function Scale will be assessed.
- Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2 [Week 25]
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).
- 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]
BOR will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1.
- BOR Based on TVS 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]
BOR will be assessed by centrally reviewed MRI scan based on TVS.
- Duration of Response (DoR) 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]
DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.
- DoR 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]
DoR will be assessed by centrally reviewed MRI scan based on TVS.
- 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]
Eligibility Criteria
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).
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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:
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Known metastatic TGCT.
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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.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nagoya University Hospital | Aichi | Japan | 466-8560 | |
| 2 | Kyushu University Hospital | Fukuoka | Japan | 812-8582 | |
| 3 | Kanazawa University Hospital | Ishikawa | Japan | 920-8641 | |
| 4 | National Hospital Organization Osaka National Hospital | Osaka | Japan | 540-0006 | |
| 5 | Osaka International Cancer Institute | Osaka | Japan | 541-8567 | |
| 6 | National Cancer Center Hospital | Tokyo | Japan | 104-0045 |
Sponsors and Collaborators
- Daiichi Sankyo Co., Ltd.
Investigators
- Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PL3397-A-J304
- jRCT2041200074