Study to Evaluate Discontinuation and Re-Treatment in Participants With Tenosynovial Giant Cell Tumor (TGCT) Previously Treated With Pexidartinib (PLX3397)

A Phase 4, Multicenter Study to Evaluate Discontinuation and Re-Treatment in Subjects With Tenosynovial Giant Cell Tumor (TGCT) Previously Treated With Pexidartinib

This study is designed to evaluate the discontinuation/re-treatment of pexidartinib therapy in previously treated participants with tenosynovial giant cell tumor (TGCT).

Study Overview

• Status: Completed
• Conditions: Tenosynovial Giant Cell Tumor
• Intervention / Treatment: Drug: Pexidartinib

Detailed Description

This multicenter study in previously pexidartinib-treated participants with TGCT will provide the Investigators and participants the option at Screening to either continue pexidartinib treatment (Treatment Continuation Cohort) or discontinue treatment with the possibility of re-initiating pexidartinib treatment (Treatment-Free/Re-Treatment Cohort).

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
  • Victoria
    • East Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Hungary
  • Budapest, Hungary, H-1062
    • Magyar Honvédség Egészségügyi Központ
• Italy
  • Bologna, Italy, 40136
    • Rizzoli-Istituto Ortopedico Rizzoli
  • Milano, Italy, 20133
    • Fondazione IRCC Istituto Nazionale dei Tumori
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center (LUMC)
• Spain
  • Barcelona, Spain, 08041
    • Hospital Sant Pau
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio
• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Currently enrolled and on pexidartinib treatment in one of the following studies: Study PLX108-10 (ENLIVEN), Study PLX108-01, Study PL3397-A-A103 or Study PL3397-A-U126.
• Willing and able to complete the PROMIS Physical Function Scale and EQ-5D-5L throughout the study.
• Willing and able to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
• Females of reproductive potential must have a negative urine pregnancy test at Screening/Baseline (to be confirmed by a serum pregnancy test taken on the last treatment visit of their prior study). They are advised to use an effective, non-hormonal method of contraception during treatment with pexidartinib and for 1 month after the last dose. Males with female partners of reproductive potential should be advised to use an effective method of contraception during treatment with pexidartinib and for 1 month after the last dose. Female partners of male patients should concurrently use effective contraceptive methods (hormonal or non-hormonal).

Note: A female is considered of reproductive potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with a confirmed by follicle stimulating hormone (FSH) test level >40 mIU/mL.

• Male participants must not freeze or donate sperm starting at Screening and throughout the study period, and for at least 5 half-lives or 1 month after the final study drug administration, whichever is longer. Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 1 month or 5 half-lives after the final study drug administration, whichever is longer.

Exclusion Criteria:

• Participant has a clinically significant abnormality identified by the Investigator at Screening on physical examination, laboratory tests, or electrocardiogram (ECG) which, in the judgement of the Investigator, would preclude the participant's safe completion of the study.
• Exposure to another investigational drug or current participation in other therapeutic investigational procedures, besides pexidartinib studies, within 1 month prior to start of study treatment. Any known contraindication to treatment with, including hypersensitivity to, the study drug(s) or excipients in pexidartinib.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Continuation Cohort; Previously-treated participants with TGCT continuing their current dose of pexidartinib treatment.	Drug: Pexidartinib; 200 mg capsules administered orally twice daily on an empty stomach (at least 1 hour before or at least 2 hours after a meal or snack); Other Names: TURALIO™️; PLX3397
Experimental: Treatment-Free/Re-Treatment Cohort; Previously-treated participants with TGCT who discontinue pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose at completion of prior study (Re-Treatment Period).	Drug: Pexidartinib; 200 mg capsules administered orally twice daily on an empty stomach (at least 1 hour before or at least 2 hours after a meal or snack); Other Names: TURALIO™️; PLX3397

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment-Free Participants at 12 Months In The Treatment-free/Re-treatment Cohort	Participants who were not remaining treatment-free were defined as either participants who resumed pexidartinib treatment, death (any cause) or who were receiving systemic therapy or undergoing surgery for the treatment of TGCT, whichever occurs first. The number of participants who remained treatment-free at Month 12 is reported.	Baseline up to 12 months after last participant enrolled in Cohort
Number of Treatment-Free Participants at 24 Months In The Treatment-free/Re-treatment Cohort	Participants who were not remaining treatment-free were defined as either participants who resumed pexidartinib treatment, death (any cause) or who were receiving systemic therapy or undergoing surgery for the treatment of TGCT, whichever occurs first. The number of participants who remained treatment-free at Month 24 is reported.	Baseline up to 24 months after last participant enrolled in Cohort

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in PROMIS Physical Function Total Overall Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts	The PROMIS Physical Function Total Overall Score (includes 11 upper extremity questions and 13 lower extremity questions) ranges from 24 to 120, with each individual question being rated on a 5-point rating scale (where 1 is unable to do and 5 is without any difficulty). Higher PROMIS Physical Function Total Overall Scores indicate a better health state. The change from baseline in PROMIS Physical Function Total Overall Scores is being reported.	Baseline up to Month 24
Change From Baseline in EQ-5D-5L Scale Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts	The EQ-5D-5L questionnaire assessed a participant's mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The overall health is rated on a scale from 0 to 100, where 0 is worst health you can imagine and 100 is best health you can imagine. The change from baseline in EQ-5D-5L Scale Score is being reported.	Baseline up to Month 24
Number of Participants With and Without Progressive Disease	Tumors were assessed based on the RECIST criteria. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; ≥30% increase in volume relative to lowest score during the study whether at baseline or some other visit.	Month 18 (Re-treatment Period of the Treatment-free/Re-treatment Cohort), Month 24 (Treatment Continuation Cohort)
Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Treatment Continuation Cohort	Treatment-emergent adverse events (TEAEs) were defined as new adverse events (AEs) or pre-existing conditions that worsen in CTCAE grade after the first dose of study drug and up to 30 days after last dose of study drug.	Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months
Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Re-Treatment Period of the Treatment-free/Re-Treatment Cohort	Treatment-emergent adverse events (TEAEs) were defined as new adverse events (AEs) or pre-existing conditions that worsen in CTCAE grade after the first dose of study drug and up to 30 days after last dose of study drug.	Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months
Number of Patients Reporting AEs (Treatment-free)	Adverse events (AEs) were defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. Participants who were not remaining treatment-free were defined as either participants who resumed pexidartinib treatment, death (any cause) or who were receiving systemic therapy or undergoing surgery for the treatment of TGCT, whichever occurs first.	Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Investigators: Study Director: Clinical Team Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Tenosynovial Giant Cell Tumor; Pexidartinib; TURALIO™️; PLX3397
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Joint Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Synovitis; Tendinopathy; Giant Cell Tumor of Tendon Sheath; Giant Cell Tumors
• Other Study ID Numbers: PL3397-A-U4003; 2020-000192-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No