Tenosynovial Giant Cell Tumor MedDRA version: 21.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Sponsors
Deciphera Pharmaceuticals, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female participants =18 years of age 2. Histologically confirmed diagnosis of TGCT (formerly known as pigmented villonodular synovitis [PVNS] or giant cell tumor of the tendon sheath [GCT-TS]). Tumor biopsy to confirm TGCT diagnosis will be required if no histology/pathology is available a. Participants should have TGCT in a single joint and must have TGCT in joints where ROM can be assessed 3. Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity as judged by surgical consultation or a multidisciplinary tumor board 4. Symptomatic disease with at least moderate pain or at least moderate stiffness (defined as a score of 4 or more, with 10 describing the worst condition) within the screening period, and documented in the medical record 5. Participant should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements outlined in Protocol Table 4 6. An analgesic regimen, if used, needs to be stable (ie, no change in dose) as judged by the Investigator for at least 2 weeks prior to the first dose of study drug 7. Measurable disease per RECIST v1.1 with at least one lesion having a minimum size of 2 cm as assessed from magnetic resonance imaging (MRI) scans by a central radiologist 8. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 21 days prior to the first dose of study drug: a. Bone marrow function: absolute neutrophil count (ANC) =1500/µL; hemoglobin =10 g/dL; platelet count = lower limit of normal (LLN) b. Hepatic function: total serum bilirubin =upper limit of normal (ULN); serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =ULN c. Renal function: creatinine clearance =50 mL/min based either on urine collection or Cockcroft-Gault estimation d. Electrolytes =LLN for: potassium, magnesium, and calcium 9. Able to take oral medication 10. Participants of reproductive potential must: a. Have a negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy test at screening (female participants) b. Agree to follow the contraception requirements outlined in the protocol 11. The participant is capable of understanding and complying with the protocol and has signed the informed consent form (ICF). A signed ICF must be obtained before any study-specific procedures are performed. 12. Willing and able to complete the PRO assessments on an electronic device Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Previous use of systemic therapy (investigational or approved) targeting CSF1 or CSF1R including vimseltinib; previous therapy with imatinib and nilotinib is allowed 2. Treatment for TGCT, including investigational therapy, during the screening period. NOTE: Participants may not be part of an ongoing or have prior participation in a non-TGCT investigational drug study within 30 days of screening. Ongoing participation in a noninterventional study (including observational studies) is permitted. 3. Known metastatic TGCT or other active cancer that requires concurrent treatment (exceptions will be considered on a case-by-case basis depending on tumor type, stage, location, planned treatment, and expected recovery after discussion and approval by Sponsor) 4. Baseline prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome 5. Receive concurrent treatment with any prohibited medications: • Acetaminophen usage exceeding 3 g/day • Proton-pump inhibitors taken within 4 days prior to the first dose of study drug • Medications that are breast cancer resistance protein (BCRP) or organic cation transporter 2 (OCT2) substrates taken within at least 4 days or 5×half-life (whichever is longer) prior to the first dose of study drug • Medications with a known risk of prolonging the QT interval within at least 14 days or 5×half-life (whichever is longer) prior to the first dose of study drug (see Appendix 1) • Prophylactic use of myeloid growth factors (eg, granulocyte colony-stimulating factor [G CSF], granulocyte macrophage-colony-stimulating factor [GM-CSF]) 6. Major surgery within 14 days of the first dose of study drug; following major surgeries >14 days prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence 7. Any clinically significant comorbidities, such as significant concomitant arthropathy not related to TGCT in the affected joint, or any other serious medical or psychiatric condition(s), known current alcohol abuse, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the participant to safety risks 8. Active liver or biliary disease including non-alcoholic steatohepatitis (NASH) or cirrhosis 9. Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator 10. Known active human immunodeficiency virus (HIV), acute or chronic hepatitis B, acute or chronic hepatitis C, or known active mycobacterium tuberculosis infection 11. If female, the participant is pregnant or breastfeeding 12. Known allergy or hypersensitivity to any component of the study drug 13. Contraindication to MRI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate anti-tumor activity of vimseltinib using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent radiological review (IRR);Secondary Objective: • To assess anti-tumor activity of vimseltinib using tumor volume score (TVS) and modified RECIST (mRECIST) by blinded IRR • To assess the effects of vimseltinib on range of motion (ROM) • To assess the effects of vimseltinib on physical function, worst stiffness, worst pain, and quality of life (QoL) using patient-reported outcome (PRO) measures • To assess safety and tolerability of vimseltinib;Primary end point(s): Objective response rate (ORR, including complete response [CR] and partial response [PR]) per RECIST v1.1 at Week 25;Timepoint(s) of evaluation of this end point: week 25 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 25 and monitored throughout the study;Secondary end point(s): Key Secondary Endpoint: • ORR per TVS at Week 25 • Change from baseline in active ROM of the affected joint, relative to a reference standard, at Week 25 • Change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25 • Change from baseline in the Worst Stiffness numeric rating scale (NRS) score at Week 25 • Change from baseline in EQ-VAS (EuroQol Visual Analogue Scale) at Week 25 • Response of at least a 30% improvement in the mean Brief Pain Inventory (BPI) Worst Pain NRS score without a 30% or greater increase in narcotic analgesic use at Week 25 Other Secondary Endpoint: • ORR per RECIST v1.1 • ORR assessed by mRECIST at Week 25 • Duration of response (DOR; time from first PR or CR to disease progression or death) assessed using RECIST v1.1, TVS, and mRECIST • Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events, related TEAEs, dose reductions, dose interruptions, and discontinuation of study drug due to adverse event • Changes from baseline in laboratory parameters, electrocardiograms (ECGs), and vital signs | — |
Countries
Australia, Canada, France, Germany, Hong Kong, Italy, Netherlands, Norway, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactRebecca Lieberman
Deciphera Pharmaceuticals, LLC
Outcome results
None listed