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A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

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ClinicalTrials.gov Identifier: NCT04703322
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : June 29, 2021
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

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
Tenosynovial Giant Cell Tumor Drug: Pexidartinib 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Two-Part, Open-Label Study of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor in Japan
Actual Study Start Date : March 15, 2021
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


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:
  • TURALIO™
  • PLX3397




Primary Outcome Measures :
  1. Dose-limiting Toxicity (DLT) in Part 1 [ Time Frame: 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.

  2. Analysis of Pharmacokinetic Parameter: Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 [ 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) ]
    Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.

  3. 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 [ 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) ]
    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.

  4. Analysis of Pharmacokinetic Parameter: Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1 [ 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) ]
    AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.

  5. Analysis of Pharmacokinetic Parameter: Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 [ 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) ]
    Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.

  6. Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2 [ Time Frame: Week 25 ]
    ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.


Secondary Outcome Measures :
  1. ORR Based on Tumor Volume Score (TVS) in Part 2 [ Time Frame: Week 25 ]
    ORR will be assessed by centrally reviewed MRI scan based on TVS.

  2. Range of Motion (ROM) in Part 2 [ Time Frame: Week 25 ]
    Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed.

  3. Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2 [ Time Frame: Week 25 ]
    Mean change from baseline score in the PROMIS Physical Function Scale will be assessed.

  4. Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2 [ Time Frame: 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).

  5. Best Overall Response (BOR) based on RECIST Version 1.1 in Part 2 [ 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 will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1.

  6. BOR Based on TVS in Part 2 [ 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 will be assessed by centrally reviewed MRI scan based on TVS.

  7. Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2 [ 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 will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.

  8. DoR 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 ]
    DoR will be assessed by centrally reviewed MRI scan based on TVS.

  9. 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 ]


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04703322


Contacts
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Contact: Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
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Japan
Nagoya University Hospital Recruiting
Aichi, Japan, 466-8560
Contact: See Central Contact         
Kyushu University Hospital Recruiting
Fukuoka, Japan, 812-8582
Contact: See Central Contact         
Kanazawa University Hospital Recruiting
Ishikawa, Japan, 920-8641
Contact: See Central Contact         
National Hospital Organization Osaka National Hospital Recruiting
Osaka, Japan, 540-0006
Contact: See Central Contact         
National Cancer Center Hospital Recruiting
Tokyo, Japan, 104-0045
Contact: See Central Contact         
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT04703322    
Other Study ID Numbers: PL3397-A-J304
jRCT2041200074 ( Other Identifier: Japan Registry of Clinical Trials )
First Posted: January 11, 2021    Key Record Dates
Last Update Posted: June 29, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Tenosynovial Giant Cell Tumor
TGCT
Giant Cell Tumor of Tendon Sheath
GCTTS
Pigmented Villonodular Synovitis
PVNS
Additional relevant MeSH terms:
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Giant Cell Tumors
Giant Cell Tumor of Tendon Sheath
Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Synovitis
Joint Diseases
Musculoskeletal Diseases
Tendinopathy
Muscular Diseases