Study of Vimseltinib for Tenosynovial Giant Cell Tumor

Phase 3

Active, not recruiting

• Conditions: Tenosynovial Giant Cell Tumor, Diffuse; Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis; Tenosynovial Giant Cell Tumor, Localized; Giant Cell Tumor of Tendon Sheath
• Interventions: Drug: Vimseltinib; Drug: Placebo

• Registration Number: NCT05059262
• Lead Sponsor: Deciphera Pharmaceuticals, LLC

Brief Summary

This is a multicenter Phase 3 clinical study, which aims to evaluate the effectiveness of an investigational drug called vimseltinib for the treatment of tenosynovial giant cell tumor (TGCT) in cases where surgical removal of the tumor is not an option.

The study consists of two parts. In Part 1, eligible study participants will be assigned to receive either vimseltinib or matching placebo for 24 weeks. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. MRI scans will be used to evaluate the response of the tumors to the treatment. Participants assigned to placebo in Part 1 will have the option to receive vimseltinib for Part 2. Part 2 is a long-term treatment phase in which all participants receive open-label vimseltinib.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-17
• Study First Submitted QC: 2021-09-17
• Study First Posted: 2021-09-28
• Study Start: 2021-10-14
• Primary Completion: 2023-08-10
• Disposition First Submitted: 2024-08-08
• Results First Submitted: 2025-01-13
• Status Verified: 2025-02
• Results First Submitted QC: 2025-02-20
• Last Update Submitted: 2025-02-20
• Results First Posted: 2025-02-24
• Disposition First Posted: 2025-02-24
• Last Update Posted: 2025-02-24
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 123

Inclusion Criteria

1. Patients ≥18 years of age
2. TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)
3. Symptomatic disease as defined as 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
4. Participants should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements as outlined in study protocol
5. Must have stable analgesic regimen, as judged by the investigator, for at least 2 weeks prior to first dose of study drug
6. Must have measurable disease, as per RECIST Version 1.1, with at least one lesion having a minimum size of 2cm
7. Adequate organ and bone marrow function
8. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements
9. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures
10. Willing and able to complete the patient-reported outcome (PRO) assessments on an electronic device

Exclusion Criteria

1. Previous use of systemic therapy (investigational or approved) targeting colony-stimulating factor 1 (CSF1) or colony-stimulating factor 1 receptor (CSF1R); previous therapy with imatinib and nilotinib is allowed
2. Received therapy for TGCT, including investigational therapy during the screening period. Participated in a non-TGCT investigational drug study within 30 days of screening.
3. Known metastatic TGCT or other active cancer that requires concurrent treatment (exceptions will be considered on a case-by-case basis)
4. QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome
5. Concurrent treatment with any study-prohibited medications
6. Major surgery within 14 days of the first dose of study drug
7. Any clinically significant comorbidities
8. Active liver or biliary disease including nonalcoholic steatohepatitis (NASH) or cirrhosis
9. Malabsorption syndrome or other illness that could affect oral absorption
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
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part 1/Part 2 - Vimseltinib/Vimseltinib	Vimseltinib	Participants received blinded treatment of 30 mg twice a week (BIW) vimseltinib for 24 weeks in Part 1 and open-label 30 mg BIW vimseltinib in Part 2.
Part 1/Part 2: Placebo/Vimseltinib	Vimseltinib	Participants received blinded treatment of BIW matching placebo for 24 weeks in Part 1 and open-label 30 mg BIW vimseltinib in Part 2.
Part 1/Part 2: Placebo/Vimseltinib	Placebo	Participants received blinded treatment of BIW matching placebo for 24 weeks in Part 1 and open-label 30 mg BIW vimseltinib in Part 2.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) at Week 25 Per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1	Baseline to Week 25 (Cycle 7, Day 1)	ORR was assessed by blinded independent radiologic review (IRR) using RECIST Version 1.1. ORR was defined as the percentage of participants who achieved either complete response (CR) or partial response (PR).; * CR: Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter (mm) in short axis. Non-nodal targets must be absent.; * PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

Name	Time	Method
ORR at Week 25 Per Tumor Volume Score (TVS)	Baseline to Week 25 (Cycle 7, Day 1)	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 CR or PR as assessed by blinded IRR using TVS.; * CR: Lesion completely gone; * PR: ≥50% decrease in volume score relative to Baseline.
Change From Baseline in Active Range of Motion (ROM) at Week 25	Baseline to Week 25 (Cycle 7, Day 1)	Presented here is the change from baseline in active 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 active 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 Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 25	Baseline to Week 25 (Cycle 7, Day 1)	All participants were asked 15 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." Total scores were converted to T-scores that ranged from 0 to 100, with higher scores representing less physical function interference and better health outcomes.
Change From Baseline in the Worst Stiffness Numeric Rating Scale (NRS) Score at Week 25	Baseline to Week 25 (Cycle 7, Day 1)	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 EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25	Baseline to Week 25 (Cycle 7, Day 1)	The EQ-VAS is a standardized tool for measuring overall health. EQ-VAS recorded the participant's self-rated health on a vertical VAS scale ranging from a minimum of 0 (worst imaginable health state) to a maximum of 100 (best imaginable health state). Higher scores indicated better health state.
Percentage of Participants With Response at Week 25 Based on Brief Pain Inventory (BPI) Worst Pain NRS Score and Narcotic Analgesic Use	Baseline to Week 25 (Cycle 7, Day 1)	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." A responder was defined as a participant who: (i) experienced a decrease of at least 30% in the mean BPI Worst Pain NRS item and (ii) did not experience a 30% or greater increase in narcotic analgesic use.

Trial Locations

Locations (35)

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Ohio State University; 🇺🇸 Columbus, Ohio, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

City of Hope; 🇺🇸 Duarte, California, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Cancer & Haematology Centre, The Churchill Hospital - Oxford University Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, Australia

Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

University College London Hospitals; 🇬🇧 London, United Kingdom

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

University of Kansas; 🇺🇸 Kansas City, Kansas, United States

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Helios Klinikum Berlin-Buch; 🇩🇪 Berlin, Germany

Prince of Wales Hospital; 🇭🇰 Hong Kong, Hong Kong

Istituto Oncologico Veneto; 🇮🇹 Padua, Italy

Istituto Nazionale Tumori Regina Elena; 🇮🇹 Rome, Italy

Oslo University Hospital; 🇳🇴 Oslo, Norway

Princess Margaret Hospital; 🇨🇦 Toronto, Canada

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Institut Gustave Roussy; 🇫🇷 Villejuif, France

University Hospital Essen (Universitätsklinikum Essen); 🇩🇪 Essen, Germany

Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy

Universitäts-Kinderspital beider Basel (UKBB); 🇨🇭 Basel, Switzerland

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut Bergonié; 🇫🇷 Bordeaux, France

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"; 🇮🇹 Naples, Italy

Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy; 🇵🇱 Warsaw, Poland

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Duke Sarcoma Research; 🇺🇸 Durham, North Carolina, United States

McGill University; 🇨🇦 Montréal, Canada