Tenosynovial Giant Cell Tumor
Conditions
Keywords
Nodular TGCT, diffuse TGCT, giant cell tumor of tendon sheath, colony-stimulating factor 1 receptor (CSF-1R) inhibitor
Brief summary
The primary purpose of this study is to assess the tolerability, pharmacokinetics, and efficacy of pimicotinib in Japanese participants with TGCT
Detailed description
The purpose of this study is to assess the tolerability, pharmacokinetics (PK), efficacy, and safety of pimicotinib in Japanese participants with TGCT in two cohorts: Safety Run-in and Expansion.
Interventions
DRUGPimicotinib
In the Safety Run-in Cohort, participants will receive 50 milligrams (mg) of pimicotinib once daily (QD), orally in 28-day cycles until disease progression (DP), death, discontinuation, or any other reason. The Safety Monitoring Committee (SMC) will monitor and assess tolerability of pimicotinib 50 mg QD during the safety run-in cohort. After making a recommendation about opening the Expansion Cohort based on the assessment in safety run-in cohort, participants will receive 50 mg of pimicotinib monotherapy QD, orally in 28-day cycles until disease progression (DP), death, discontinuation, or any other reason.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Japanese participants with a diagnosis of TGCT that has been histologically confirmed at the local laboratory and is unresectable (that is \[i.e.\] it is located in a complex anatomical site, extensively invasive, and cannot be completely resected; or a surgical operation may cause dysfunction or serious complications). Symptomatic disease because of active TGCT, defined as a worst pain of greater than or equal to \[\>=\] 4 within 2 weeks prior to enrollment (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine"), and/or a worst stiffness of \>= 4 within 2 weeks prior to first dose of pimicotinib (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine") * Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to \[\<=\] 1 * Participants with adequate hepatic, renal hematologic functions * Other protocol defined inclusion criteria may apply
Exclusion criteria
* Known additional malignancy that required active treatment and may affect the participant's participation in the study or affect the outcome of the study as assessed by the Investigator. Exceptions include cured basal cell carcinoma of skin, squamous cell carcinoma of skin, and other carcinoma in situ * Serious gastrointestinal bleeding within 3 months of first dose of pimicotinib or factors that significantly affected the absorption of oral drug, such as inability to take oral medication or significant nausea and vomiting, malabsorption, external bile duct drainage, massive small-bowel resection, etc. * Impaired cardiac function or clinically significant cardiac disease, including any one of the following: New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure; prolongation of the rate corrected QT interval based on repeated demonstration of QT interval corrected using Fridericia's formula (QTcF) greater than (\>) 480 milliseconds (ms), or history of long QT interval corrected (QTc) syndrome; Left ventricular ejection fraction (LVEF) less than (\<) 50 percent (%) or below the lower limit of normal, whichever is higher * Cerebrovascular accident/stroke (within 6 months of first dose of pimicotinib) * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Run-In Cohort: Number of Participants with Dose Limiting Toxicity (DLT)-like events | Day 1 up to Day 28 of Cycle 1 (each cycle is of 28 days) |
| Safety Run-In Cohort: Pharmacokinetic (PK) Plasma Concentration of Pimicotinib | Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is of 28 days) |
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee | Time from first study treatment until progressive disease or death, assessed up to approximately 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (OR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC) | Time from first study treatment until progressive disease or death, assessed up to approximately 2 years | — |
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator | Time from first study treatment until progressive disease or death, assessed up to approximately 2 years | — |
| Mean Change from Baseline in Range of Motion (ROM) at Week 25 | Baseline, Week 25 | The ROM of the affected joint or tumor site will be assessed using a goniometer. Measurements will be recorded in degrees. |
| Mean Change from Baseline in Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25 | Baseline, Week 25 | — |
| Mean Change from Baseline in Brief Pain Inventory (BPI)- Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25 | Baseline, Week 25 | — |
| Mean Change from Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Physical Functioning Score at Week 25 | Baseline, Week 25 | The PROMIS Physical Function scale is measured using a series of questions assessing a person's ability to perform various physical tasks, with responses scored on a 5-point Likert scale. The raw score from these responses is then converted to a standardized T-score on a scale of 0 to 100, with a mean of 50 and a standard deviation of 10. The total score is the final T-score. |
| Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee | Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years | — |
| Duration of Response (DOR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC) | Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years | — |
| Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator | Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years | — |
| Mean Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Scale Score at Week 25 | Baseline, Week 25 | The EQ-5D-5L questionnaire is a standardized instrument used as a measure of health outcome. The 5-dimension health status measure evaluates: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: an extreme problem. Higher scores (closer to 5) indicate worse health status. |
| Mean Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score at Week 25 | Baseline, Week 25 | The EQ-5D-5L questionnaire is a standardized instrument used as a measure of health outcome. The VAS records the participant's self-rated health on a vertical VAS where the endpoints are labelled 'Worst imaginable health state' and 'Best imaginable health state'. VAS ranges from 0 to 100. Higher scores indicate better perceived health. |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events | Time from first study treatment, assessed up to approximately 2 years | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pimicotinib | Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is of 28 days) | — |
| Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Pimicotinib After Repeated Administration | Pre-dose up to 24 hours post-dose on Cycle 1 Day 15 (each cycle is of 28 days) | — |
| Accumulation Ratio of Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC0-24) of Pimicotinib After Repeated Administration | Pre-dose up to 24 hours post-dose on Cycle 1 Day 15 (each cycle is of 28 days) | — |
| Plasma Concentration Observed at the End of a Dosing Interval Immediately before Next Dosing (Ctrough) of Pimicotinib | Pre-dose on Cycle 1 Day 15 (each cycle is of 28 days) | — |
Countries
Japan
Contacts
CONTACTCommunication Center
STUDY_DIRECTORMedical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Outcome results
None listed