PLX3397: Study to Evaluate Discontinuation and Re-Treatment in Participants With Tenosynovial Giant Cell Tumor (TGCT) Previously Treated With Pexidartinib
Study Details
Study Description
Brief Summary
This study is designed to evaluate the discontinuation/re-treatment of pexidartinib therapy in previously treated participants with tenosynovial giant cell tumor (TGCT).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 Design
Arms and Interventions
| 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:
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| 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:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Treatment-Free Participants at 12 Months [Baseline up to 12 months after last participant enrolled in Cohort]
This is the proportion of participants who remain treatment-free at Month 12.
- Proportion of Treatment-Free Participants at 24 Months [Baseline up to 24 months after last participant enrolled in Cohort]
This is the proportion of participants who remain treatment-free at Month 24.
Secondary Outcome Measures
- Change From Baseline in PROMIS Physical Function Scale during the Treatment-Free Period [Baseline and then assessed every 3 months until end of study, up to approximately 24 months]
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.
- Change From Baseline in EQ-5D-5L during the Treatment-Free Period [Baseline and then assessed every 3 months until end of study, up to approximately 24 months]
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.
- Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) during the Treatment-free Period [Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to approximately 24 months]
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.
- Percentage of Participants Achieving Tumor Response as assessed by Magnetic Resonance Imaging (MRI) [Baseline and assessed every 6 months (treatment continuation) or every 3 months (treatment-free/re-treatment), up to approximately 24 months]
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.
- Number of Participants Who Reported TEAEs during the Re-treatment Period [Start of re-treatment up to 30 days after end of study, up to approximately 24 months]
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.
Eligibility Criteria
Criteria
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.
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Willing and able to complete the PROMIS Physical Function Scale and EQ-5D-5L throughout the study.
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Willing and able to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
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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:
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Honor Health | Scottsdale | Arizona | United States | 85258 |
| 2 | USC Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
| 3 | Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
| 4 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 5 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 6 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 7 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 8 | Chris O'Brien Lifehouse | Camperdown | New South Wales | Australia | 2050 |
| 9 | Peter MacCallum Cancer Centre | East Melbourne | Victoria | Australia | 3000 |
| 10 | Magyar Honvedseg Egeszsegugyi Kozpont | Budapest | Hungary | H-1062 | |
| 11 | Rizzoli-Istituto Ortopedico Rizzoli | Bologna | Italy | 40136 | |
| 12 | Fondazione IRCC Istituto Nazionale dei Tumori | Milano | Italy | 20133 | |
| 13 | Leiden University Medical Center (LUMC) | Leiden | Netherlands | 2333 ZA | |
| 14 | Hospital Sant Pau | Barcelona | Spain | 08041 | |
| 15 | Hospital Virgen del Rocio | Sevilla | Spain | 41013 | |
| 16 | National Taiwan University Hospital | Taipei | Taiwan |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
- Study Director: Clinical Team Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PL3397-A-U4003
- 2020-000192-20