Clinical Trials /

A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

NCT04703322

Description:

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.

Related Conditions:
  • Tenosynovial Giant Cell Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04703322

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: PL3397-A-J304
  • SECONDARY ID: jRCT2041200074
  • NCT ID: NCT04703322

Conditions

  • Tenosynovial Giant Cell Tumor

Interventions

DrugSynonymsArms
PexidartinibTURALIO™, PLX3397Pexidartinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PexidartinibExperimentalParticipants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]).
  • Pexidartinib

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.
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting Toxicity (DLT) in Part 1
Time Frame:Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)
Safety Issue:
Description:The number of participants with dose-limiting toxicities will be assessed.

Secondary Outcome Measures

Measure:ORR Based on Tumor Volume Score (TVS) in Part 2
Time Frame:Week 25
Safety Issue:
Description:ORR will be assessed by centrally reviewed MRI scan based on TVS.
Measure:Range of Motion (ROM) in Part 2
Time Frame:Week 25
Safety Issue:
Description:Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed.
Measure:Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2
Time Frame:Week 25
Safety Issue:
Description:Mean change from baseline score in the PROMIS Physical Function Scale will be assessed.
Measure:Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2
Time Frame:Week 25
Safety Issue:
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).
Measure: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
Safety Issue:
Description:BOR will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1.
Measure: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
Safety Issue:
Description:BOR will be assessed by centrally reviewed MRI scan based on TVS.
Measure: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
Safety Issue:
Description:DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.
Measure: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
Safety Issue:
Description:DoR will be assessed by centrally reviewed MRI scan based on TVS.
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo Co., Ltd.

Trial Keywords

  • Tenosynovial Giant Cell Tumor
  • TGCT
  • Giant Cell Tumor of Tendon Sheath
  • GCTTS
  • Pigmented Villonodular Synovitis
  • PVNS

Last Updated

June 29, 2021