This is a multicenter, randomized, Phase 3 study with vimseltinib or placebo in patients with Tenosynovial Giant Cell Tumor, consisting of 2 parts: Part 1 is double blinded and Part 2 is open label study
- Conditions
- Tenosynovial Giant Cell TumorTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004883-25-PL
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
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 per BPI Worst Pain or at least moderate stiffness per Worst Stiffness NRS item (defined as a score of 4 or more, with 10 describing the worst condition) within the screening period, prior to the first dose, 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 tumor 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: serum creatinine =1.5×ULN or 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
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 evidence of fatty liver, 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate anti-tumor activity of vimseltinib using Response Evaluation<br>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<br>• To assess the effects of vimseltinib on range of motion (ROM)<br>• To assess the effects of vimseltinib on physical function, worst stiffness, worst pain, and quality of life (QoL) using patient-reported outcome (PRO) measures<br>• 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 Outcome Measures
Name Time Method