Tenosynovial Giant Cell Tumor
Conditions
Keywords
Tenosynovial Giant Cell Tumor, Pexidartinib, TURALIO™️, PLX3397
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).
Interventions
DRUGPexidartinib
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)
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Free Participants at 12 Months In The Treatment-free/Re-treatment Cohort | Baseline 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 Cohort | Baseline 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With and Without Progressive Disease | Month 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 Cohort | Baseline 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. |
| Change From Baseline in PROMIS Physical Function Total Overall Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts | Baseline 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. |
| 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. |
| Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Re-Treatment Period of the Treatment-free/Re-Treatment Cohort | Baseline 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. |
| Change From Baseline in EQ-5D-5L Scale Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts | Baseline 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. |
Countries
Australia, Hungary, Italy, Netherlands, Spain, Taiwan, United States
Participant flow
Recruitment details
A total of 32 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study.
Pre-assignment details
As specified in the protocol, the study analysis was conducted based on 2 cohorts: Treatment Continuation Cohort and Treatment-Free/Re-Treatment Cohort.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Continuation Cohort Previously-treated participants with TGCT who continued their current dose of pexidartinib treatment. | 21 |
| Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period). | 11 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Treatment-Free/Re-Treatment Cohort | Treatment Continuation Cohort | Total |
|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 15.2 | 46.2 years STANDARD_DEVIATION 15.7 | 48.2 years STANDARD_DEVIATION 15.5 |
| Age, Customized 18 to 40 years | 1 Participants | 7 Participants | 8 Participants |
| Age, Customized 41 to 64 years | 8 Participants | 12 Participants | 20 Participants |
| Age, Customized 65 to 74 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized 75 to 84 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized ≥ 85 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not collected per local regulations | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 19 Participants | 27 Participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 16 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 3 | 0 / 11 |
| other Total, other adverse events | 19 / 21 | 3 / 3 | 7 / 11 |
| serious Total, serious adverse events | 2 / 21 | 0 / 3 | 0 / 11 |
Outcome results
Primary
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.
Time frame: Baseline up to 12 months after last participant enrolled in Cohort
Population: The number of treatment-free participants was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Number of Treatment-Free Participants at 12 Months In The Treatment-free/Re-treatment Cohort | 8 Participants |
Primary
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.
Time frame: Baseline up to 24 months after last participant enrolled in Cohort
Population: The number of treatment-free participants was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Number of Treatment-Free Participants at 24 Months In The Treatment-free/Re-treatment Cohort | 8 Participants |
Secondary
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.
Time frame: Baseline up to Month 24
Population: EQ-5D-5L was assessed in participants with available data in the Evaluable Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Change From Baseline in EQ-5D-5L Scale Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts | -2.4 score on a scale | Standard Deviation 13.53 |
| Treatment-Free/Re-Treatment Cohort | Change From Baseline in EQ-5D-5L Scale Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts | 3.4 score on a scale | Standard Deviation 7.59 |
Secondary
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.
Time frame: Baseline up to Month 24
Population: PROMIS Physical Function was assessed in participants with available data in the Evaluable Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Change From Baseline in PROMIS Physical Function Total Overall Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts | -2.78 score on a scale | Standard Deviation 6.42 |
| Treatment-Free/Re-Treatment Cohort | Change From Baseline in PROMIS Physical Function Total Overall Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts | -1.93 score on a scale | Standard Deviation 4.8 |
Secondary
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.
Time frame: Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months
Population: Treatment-emergent adverse events were assessed in participants with available data in the Safety Analysis Set .
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Re-Treatment Period of the Treatment-free/Re-Treatment Cohort | 3 Participants |
Secondary
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.
Time frame: Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months
Population: Treatment-emergent adverse events were assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Treatment Continuation Cohort | 19 Participants |
Secondary
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.
Time frame: Month 18 (Re-treatment Period of the Treatment-free/Re-treatment Cohort), Month 24 (Treatment Continuation Cohort)
Population: Tumor assessments were analyzed in participants with available data in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Number of Participants With and Without Progressive Disease | Not progressive | 16 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Participants With and Without Progressive Disease | Progressive disease | 0 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Participants With and Without Progressive Disease | Not evaluable | 0 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Participants With and Without Progressive Disease | Not progressive | 0 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Participants With and Without Progressive Disease | Progressive disease | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Participants With and Without Progressive Disease | Not evaluable | 0 Participants |
Secondary
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.
Time frame: Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months
Population: Adverse events were assessed in the Safety Analysis Set in participants with available data in the Treatment-free Period of the Treatment-Free/Re-Treatment Cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade AE | 7 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Musculoskeletal/Tissue Disorders | 6 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Arthralgia | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Back pain | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Intervertebral disc protrusion | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Joint swelling | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Musculoskeletal pain | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Pain in extremity | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Metabolism and Nutrition Disorders | 3 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Hypercholesterolaemia | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Hypertriglyceridaemia | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade General Disorders & Site Conditions | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Asthenia | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Oedema peripheral | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Infections and Infestations | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Cellulitis | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade COVID-19 | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade investigations | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Gr Blood creatinine phosphokinase increased | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Blood uric acid increased | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Renal and Urinary Disorders | 2 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Renal colic | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Urinary retention | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Injury, Poisoning & Procedural Issues | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Animal bite | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Neoplasms Benign, Malignant & Other | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Lipoma | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Nervous System Disorders | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Sciatica | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Skin and Subcutaneous Tissue Disorders | 1 Participants |
| Treatment-Free/Re-Treatment Cohort | Number of Patients Reporting AEs (Treatment-free) | Any Grade Urticaria | 1 Participants |