Giant Cell Tumor of Tendon Sheath, Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor
Conditions
Brief summary
The goal of this clinical trial is to assess the efficacy and safety of Pimicotinib (ABSK021) in patients with Tenosynovial Giant Cell Tumor (TGCT). The main questions it aims to answer are: * Whether the Pimicotinib(ABSK021) works well in patients with TGCT. * Whether the Pimicotinib(ABSK021) is safe in patients with TGCT. Participants will be asked to complete the study procedures: * Receive the administration of Pimicotinib(ABSK021) or placebo (a placebo is a look-alike substance that contains no active drug) about 24 weeks in study part 1. * Receive the administration of Pimicotinib(ABSK021) about 24 weeks in study part 2. * Receive the administration of Pimicotinib(ABSK021) till study end in study part 3. * Complete the study procedures speficied in the protocol, which is guided by researchers.
Detailed description
This study consists of part 1 and part 2. Part 1 is a double-blind phase, eligible patients will be randomized to Pimicotinib(ABSK021) treatment group or matching placebo group and will receive Pimicotinib(ABSK021) or matching placebo until completion of Part 1. Part 2 is an open-label treatment phase, and all patients entering this phase will receive open-label Pimicotinib(ABSK021) until completion of 24 weeks of dosing or withdrawal from the study. Part 3 is an open-label extension treatment phase, and patients who completed the part 2 and continuted to be eligible, will go to the Part 3. Patients will receive the open-label Pimicotinib(ABSK021) until all patients withdraw from the study, or the sponsor decides to terminate the study, whichever occurs first.
Interventions
DRUGPimicotinib(ABSK021)
capsule
DRUGPlacebo
capsule
Sponsors
Abbisko Therapeutics Co, Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients should understand the study procedures and sign the informed consent form prior to screening. * Age ≥ 18 years. * A histologically confirmed TGCT with unresectable. * Measurable disease as defined by RECIST 1.1, and with at least one lesion of ≥ 2 cm. * Stable prescription of analgesic regimen for patients with an analgesic need. * Participants should complete stiffness and pain scales during the screening period, and symptomatic disease because of active TGCT should meet minimum requirements as outlined in study protocol. * ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1. * Adequate organ function and bone marrow function.
Exclusion criteria
* Known allergy or hypersensitivity to any components of the investigational drug product. * Previous treatment with highly selective inhibitors targeting CSF-1/CSF-1R. Previous therapy with imatinib and nilotinib is allowed. * Known additional malignancy that required active treatment and may affect the patient's participation in the study or affect the outcome of the study as assessed by the Investigator. * Known metastatic TGCT. * Significant concomitant arthropathy in the affected joint, serious disease, uncontrolled infection. * Known MRI contraindications. * Has factors that significantly affected the absorption of oral drug. * Major surgery or previous anti-tumor therapy for TGCT within 4 weeks prior to randomization. * Concomitant use of strong CYP inhibitors or inducers as outlined in study protocol. * Impaired cardiac function or clinically significant cardiac disease. * Known active human immunodeficiency virus, active hepatitis B, active hepatitis C, or known active tuberculosis. * Known active liver or biliary disease, or other diseases that may lead to abnormal liver function test results during the study. * Pregnant or lactating women. * Childbearing potential males or non-surgically sterilized female patients must agree to use effective methods of contraception during the study. * Any other clinically significant comorbidities, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Baseline to Week 25 | Assessed by central read using Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Tumor Volumn Score (TVS) | Baseline to Week 25 | TVS is a semi-quantitative magnetic resonance imaging (MRI) scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. ORR was the percentage of participants who achieved either Complete Response (CR) or Partial Response (PR) as assessed by Blinded Independent Review Committee using TVS. |
| Change From Baseline in Active Range of Motion (ROM) at Week 25 | Baseline to Week 25 | Presented here is the change from baseline in ROM to Week 25. Measurement of the affected and contralateral, non-affected joint was assessed by goniometer and measured in degrees. At baseline, the motion with the smallest relative ROM value (worst) was identified, and this motion was used for evaluating the change in relative ROM subsequently. The affected joint measurement was used to derive a relative ROM based on the measurement relative to reference standard value provided by the American Medical Association. Relative ROM is expressed in percent: 100 x (joint ROM measure)/(reference ROM standard). |
| Change From Baseline in the Worst Stiffness Numeric Rating Scale (NRS) Score at Week 25 | Baseline to Week 25 | The Worst Stiffness NRS is a single question that asks the participant to assess their worst stiffness in the last 24 hours. Participants rate their worst stiffness on a scale of 0 to 10, where 0 is "no stiffness" and 10 is "worst imaginable." Lower scores represented better level of stiffness. |
| Change From Baseline in Brief Pain Inventory (BPI) Worst Pain NRS Score at Week 25 | Baseline to Week 25 | Participants reported responses to the BPI Worst Pain NRS. The BPI Worst Pain NRS ranged from 0 to 10, where 0 is "no pain" and 10 is "pain as bad as you can imagine." |
| Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 25 | Baseline to Week 25 | All participants were asked 11 or 13 questions from the PROMIS-PF item bank. The questions used one of two 5-point verbal rating scales: either 1 = "unable to do", 2 = "with much difficulty", 3 = "with some difficulty", 4 = "with a little difficulty", and 5 = "without any difficulty"; or 1 = "cannot do", 2 = "quite a lot", 3 = "somewhat", 4 = "very little", and 5 = "not at all." The T-score rescales the total raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person with a T-score of 40 is one SD below the mean. The T-score ranges from 0 to 100, with a higher score indicating better physical function status. |
Countries
Canada, China, Italy, Netherlands, Poland, Spain, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 12.46 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 32 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 37 Participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment China | 14 participants |
| Region of Enrollment Italy | 2 participants |
| Region of Enrollment Netherlands | 5 participants |
| Region of Enrollment Poland | 0 participants |
| Region of Enrollment Spain | 10 participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 31 |
| other Total, other adverse events | 62 / 63 | 27 / 31 |
| serious Total, serious adverse events | 3 / 63 | 1 / 31 |
Outcome results
None listed