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 Honvedseg Egeszsegugyi Kozpont
• 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 Rocío
• 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 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
Proportion of Treatment-Free Participants at 12 Months	This is the proportion of participants who remain treatment-free at Month 12.	Baseline up to 12 months after last participant enrolled in Cohort
Proportion of Treatment-Free Participants at 24 Months	This is the proportion of participants who remain treatment-free at Month 24.	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 Scale during the Treatment-Free Period	The PROMIS Physical Function Scale is based on a 5-point rating scale, where 1 is unable to do and 5 is without any difficulty.	Baseline and then assessed every 3 months until end of study, up to approximately 24 months
Change From Baseline in EQ-5D-5L during the Treatment-Free Period	The EQ-5D-5L questionnaire will ask the participant to describe their health in the areas of 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.	Baseline and then assessed every 3 months until end of study, up to approximately 24 months
Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) during the Treatment-free Period	TEAEs are defined as new Adverse Events 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 approximately 24 months
Percentage of Participants Achieving Tumor Response as assessed by Magnetic Resonance Imaging (MRI)	Individual participant outcomes by tumor volume score (TVS) will be classified according to the following criteria via RECIST: Complete response (CR), Lesion completely gone; Partial response (PR), ≥50% decrease in volume score relative to baseline; Progressive disease (PD), ≥30% increase in volume relative to lowest score during the study whether at baseline or some other visit; Stable disease (SD), Does not meet any of the prior criteria based on score during study.	Baseline and assessed every 6 months (treatment continuation) or every 3 months (treatment-free/re-treatment), up to approximately 24 months
Number of Participants Who Reported TEAEs during the Re-treatment Period	TEAEs are defined as new Adverse Events 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.	Start of re-treatment up to 30 days after end of study, up to approximately 24 months

Collaborators and Investigators

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

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): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Tenosynovial Giant Cell Tumor; Pexidartinib; TURALIO™️; PLX3397
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath
• 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