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

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

Detailed Description
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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).

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

Conditions
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Tenosynovial Giant Cell Tumor

Intervention / Treatment
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* Drug: Pexidartinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Continuation Cohort<br>Previously-treated participants with TGCT continuing their current dose of pexidartinib treatment. | Drug: Pexidartinib<br>* 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)<br>* Other names: PLX3397;|
| Experimental: Treatment-Free/Re-Treatment Cohort<br>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<br>* 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)<br>* Other names: PLX3397;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tenosynovial Giant Cell Tumor, Pexidartinib, TURALIO™️, PLX3397