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

Phase 4
Completed
Conditions
Tenosynovial Giant Cell Tumor
Interventions
Registration Number
NCT04526704
Lead Sponsor
Daiichi Sankyo
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).

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment Continuation CohortPexidartinibPreviously-treated participants with TGCT continuing their current dose of pexidartinib treatment.
Treatment-Free/Re-Treatment CohortPexidartinibPreviously-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).
Primary Outcome Measures
NameTimeMethod
Number of Treatment-Free Participants at 12 Months In The Treatment-free/Re-treatment CohortBaseline up to 12 months after last participant enrolled in 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.

Number of Treatment-Free Participants at 24 Months In The Treatment-free/Re-treatment CohortBaseline up to 24 months after last participant enrolled in 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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in PROMIS Physical Function Total Overall Score In The Treatment Continuation and Treatment-free/Re-Treatment CohortsBaseline up to Month 24

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.

Change From Baseline in EQ-5D-5L Scale Score In The Treatment Continuation and Treatment-free/Re-Treatment CohortsBaseline up to Month 24

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.

Number of Participants With and Without Progressive DiseaseMonth 18 (Re-treatment Period of the Treatment-free/Re-treatment Cohort), Month 24 (Treatment Continuation Cohort)

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.

Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Treatment Continuation CohortBaseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

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.

Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Re-Treatment Period of the Treatment-free/Re-Treatment CohortBaseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

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.

Number of Patients Reporting AEs (Treatment-free)Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

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.

Trial Locations

Locations (16)

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Leiden University Medical Center (LUMC)

🇳🇱

Leiden, Netherlands

Washington University

🇺🇸

Saint Louis, Missouri, United States

Hospital Virgen del Rocio

🇪🇸

Sevilla, Spain

Rizzoli-Istituto Ortopedico Rizzoli

🇮🇹

Bologna, Italy

USC Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Sylvester Comprehensive Cancer Center

🇺🇸

Miami, Florida, United States

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Hospital Sant Pau

🇪🇸

Barcelona, Spain

Honor Health

🇺🇸

Scottsdale, Arizona, United States

Fondazione IRCC Istituto Nazionale dei Tumori

🇮🇹

Milano, Italy

Magyar Honvedseg Egeszsegugyi Kozpont

🇭🇺

Budapest, Hungary

Chris O'Brien Lifehouse

🇦🇺

Camperdown, New South Wales, Australia

Peter MacCallum Cancer Centre

🇦🇺

East Melbourne, Victoria, Australia

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

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