E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Tenosynovial giant cell tumor (TGCT) is a group of neoplasms including pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS) |
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E.1.1.1 | Medical condition in easily understood language |
Tenosynovial giant cell tumour is a condition where the tissue surrounding the joints and tendons, called the synovial lining or synovium, expands abnormally forming outgrowths of the joint. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062856 |
E.1.2 | Term | Giant cell tumour of tendon sheath benign |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Proportion of subjects who remain treatment-free. |
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E.2.2 | Secondary objectives of the trial |
- Change from Baseline in Patient Reported Outcomes (PROs) (PROMIS PF, EQ-5D-5L)
- Safety: Total number of subjects in the safety analysis set with any AE collected between Screening and start of re-treatment or final database lock (whichever occurs first)
- Tumor Assessment: Investigator evaluation of tumor |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria to be eligible for enrollment into the study:
1. Currently enrolled and have not been discontinued from pexidartinib treatment in one of the following studies: Study PLX108-10 (ENLIVEN), Study PLX108-01, Study PL3397-A-A103, or Study PL3397-A-U126.
2. Willing and able to complete the PROMIS (Physical Function Scale) and EQ-5D-5L (European Quality of Life) throughout the study.
3. Willing and able to provide written informed consent form (ICF) prior to any study-related procedures and to comply with all study requirements.
4. 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 End-of-Treatment visit of their prior study) and should be 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.
5. Male subjects 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 subjects 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.
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria are NOT eligible for enrollment into the study
1. Subject has a clinically significant abnormality identified by the Investigator at Screening on physical examination, laboratory tests, or electrocardiogram which, in the judgement of the Investigator, would preclude the subject’s safe completion of the study.
2. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who remain treatment-free at Month 12 and Month 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 months after last subject enrolled in the Cohort |
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E.5.2 | Secondary end point(s) |
Change from Baseline in Patient Reported Outcomes (PROs): Mean change from Baseline* for PROMIS PF and EQ-5D-5L quarterly for the treatment-free and Re-Treatment periods.
*Note: Baseline is Screening values for Treatment Free Period Treatment Continuation Cohort. Baseline is reinitiated with subject entering Re-Treatment period.
Safety: Incidence of AEs/TEAEs and SAEs, ECGs, and laboratory assessments
Tumor Assessment: Qualitative assessment of the tumor (not applicable to Treatment-Free period) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from Baseline in Patient Reported Outcomes (PROs): every 3 months
Safety:
- Incidence of AEs/TEAEs and SAEs: after subject signs the ICF and up to 30 days after the last dose of study medication
- ECGs: at screening/baseline and at EOS/EOT/FU (and whenever deemed medically necessary)
- laboratory assessments - from baseline, every study visit until EOS/EOT/FU; only for Treatment Free Period: at baseline and then every 6 months until EOS/EOT/FU |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Hungary |
Italy |
Netherlands |
Spain |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |