Back to resultsA Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan
Primary Purpose
Tenosynovial Giant Cell Tumor
Status
Recruiting
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Pexidartinib
Sponsored by
About this trial
This is an interventional treatment trial for Tenosynovial Giant Cell Tumor focused on measuring Tenosynovial Giant Cell Tumor, TGCT, Giant Cell Tumor of Tendon Sheath, GCTTS, Pigmented Villonodular Synovitis, PVNS
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.
Sites / Locations
- Nagoya University HospitalRecruiting
- Kyushu University HospitalRecruiting
- Kanazawa University HospitalRecruiting
- National Hospital Organization Osaka National Hospital
- Osaka International Cancer InstituteRecruiting
- National Cancer Center HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pexidartinib
Arm Description
Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]).
Outcomes
Primary Outcome Measures
Dose-limiting Toxicity (DLT) in Part 1
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
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
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
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
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
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
ORR will be assessed by centrally reviewed MRI scan based on TVS.
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.
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.
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).
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.
BOR Based on TVS in Part 2
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
DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.
DoR Based on TVS
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
Full Information
NCT ID
NCT04703322
First Posted
December 22, 2020
Last Updated
July 11, 2023
Sponsor
Daiichi Sankyo Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04703322
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2021 (Actual)
Primary Completion Date
February 28, 2025 (Anticipated)
Study Completion Date
November 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tenosynovial Giant Cell Tumor
Keywords
Tenosynovial Giant Cell Tumor, TGCT, Giant Cell Tumor of Tendon Sheath, GCTTS, Pigmented Villonodular Synovitis, PVNS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pexidartinib
Arm Type
Experimental
Arm Description
Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]).
Intervention Type
Drug
Intervention Name(s)
Pexidartinib
Other Intervention Name(s)
TURALIO™, PLX3397
Intervention Description
400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)
Primary Outcome Measure Information:
Title
Dose-limiting Toxicity (DLT) in Part 1
Description
The number of participants with dose-limiting toxicities will be assessed.
Time Frame
Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)
Title
Analysis of Pharmacokinetic Parameter: Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1
Description
Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.
Time Frame
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)
Title
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
Description
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
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)
Title
Analysis of Pharmacokinetic Parameter: Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1
Description
AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.
Time Frame
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)
Title
Analysis of Pharmacokinetic Parameter: Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1
Description
Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.
Time Frame
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)
Title
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2
Description
ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.
Time Frame
Week 25
Secondary Outcome Measure Information:
Title
ORR Based on Tumor Volume Score (TVS) in Part 2
Description
ORR will be assessed by centrally reviewed MRI scan based on TVS.
Time Frame
Week 25
Title
Range of Motion (ROM) in Part 2
Description
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
Title
Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2
Description
Mean change from baseline score in the PROMIS Physical Function Scale will be assessed.
Time Frame
Week 25
Title
Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2
Description
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
Title
Best Overall Response (BOR) based on RECIST Version 1.1 in Part 2
Description
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
Title
BOR Based on TVS in Part 2
Description
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
Title
Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2
Description
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
Title
DoR Based on TVS
Description
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
Title
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 3 years 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daiichi Sankyo Contact for Clinical Trial Information
Phone
+81-3-6225-1111(M-F 9-5 JST)
Email
dsclinicaltrial@daiichisankyo.co.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Nagoya University Hospital
City
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
See Central Contact
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
See Central Contact
Facility Name
Kanazawa University Hospital
City
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
See Central Contact
Facility Name
National Hospital Organization Osaka National Hospital
City
Osaka
ZIP/Postal Code
540-0006
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Osaka International Cancer Institute
City
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
See Central Contact
Facility Name
National Cancer Center Hospital
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
See Central Contact
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan
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