Study of Vimseltinib for Tenosynovial Giant Cell Tumor (MOTION)

A Phase 3, Randomized, Placebo-controlled, Double-blind Study of Vimseltinib to Assess the Efficacy and Safety in Patients With Tenosynovial Giant Cell Tumor (MOTION)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tenosynovial Giant Cell Tumor; Giant Cell Tumor of Tendon Sheath; Pigmented Villonodular Synovitis; Tenosynovial Giant Cell Tumor, Diffuse; Tenosynovial Giant Cell Tumor, Localized
• Intervention / Treatment: Drug: Placebo; Drug: Vimseltinib

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
    • Chris O'Brien Lifehouse
• Canada
  • Montreal, Canada
    • McGill University
  • Toronto, Canada
    • Princess Margaret Hospital
• France
  • Bordeaux, France
    • Institut Bergonie
  • Lyon, France
    • Centre Leon Berard
  • Villejuif, France
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany
    • Helios Klinikum Berlin-Buch
  • Essen, Germany
    • University Hospital Essen (Universitätsklinikum Essen)
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Bologna, Italy
    • Istituto Ortopedico Rizzoli
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Naples, Italy
    • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
  • Padua, Italy
    • Istituto Oncologico Veneto
  • Rome, Italy
    • Istituto Nazionale Tumori Regina Elena
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• Poland
  • Warsaw, Poland
    • Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
• Spain
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Clinico San Carlos
• Switzerland
  • Basel, Switzerland
    • Universitäts-Kinderspital beider Basel (UKBB)
• United Kingdom
  • London, United Kingdom
    • University College London Hospitals
  • London, United Kingdom
    • Cancer & Haematology Centre, The Churchill Hospital - Oxford University Hospitals NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10016
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Sarcoma Research
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1/Part 2 - 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.	Drug: Vimseltinib; Administered orally; Other Names: DCC-3014
Placebo Comparator: Part 1/Part 2: Placebo/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.	Drug: Placebo; Administered orally; Drug: Vimseltinib; Administered orally; Other Names: DCC-3014

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) at Week 25 Per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1	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.	Baseline to Week 25 (Cycle 7, Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at Week 25 Per Tumor Volume Score (TVS)	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.	Baseline to Week 25 (Cycle 7, Day 1)
Change From Baseline in Active Range of Motion (ROM) at Week 25	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).	Baseline to Week 25 (Cycle 7, Day 1)
Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 25	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.	Baseline to Week 25 (Cycle 7, Day 1)
Change From Baseline in the Worst Stiffness Numeric Rating Scale (NRS) Score at 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.	Baseline to Week 25 (Cycle 7, Day 1)
Change From Baseline in EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25	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.	Baseline to Week 25 (Cycle 7, Day 1)
Percentage of Participants With Response at Week 25 Based on Brief Pain Inventory (BPI) Worst Pain NRS Score and Narcotic Analgesic Use	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.	Baseline to Week 25 (Cycle 7, Day 1)

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals, LLC

Publications and helpful links

General Publications

• Gelderblom H, Bhadri V, Stacchiotti S, Bauer S, Wagner AJ, van de Sande M, Bernthal NM, Lopez Pousa A, Razak AA, Italiano A, Ahmed M, Le Cesne A, Tinoco G, Boye K, Martin-Broto J, Palmerini E, Tafuto S, Pratap S, Powers BC, Reichardt P, Casado Herraez A, Rutkowski P, Tait C, Zarins F, Harrow B, Sharma MG, Ruiz-Soto R, Sherman ML, Blay JY, Tap WD; MOTION investigators. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jun 22;403(10445):2709-2719. doi: 10.1016/S0140-6736(24)00885-7. Epub 2024 Jun 3.
• Tap WD, Sharma MG, Vallee M, Smith BD, Sherman ML, Ruiz-Soto R, de Sande MV, Randall RL, Bernthal NM, Gelderblom H. The MOTION study: a randomized, phase III study of vimseltinib for the treatment of tenosynovial giant cell tumor. Future Oncol. 2024 Mar;20(10):593-601. doi: 10.2217/fon-2023-0238. Epub 2023 Aug 18.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2021
• Primary Completion (Actual): August 10, 2023
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: TGCT; PVNS
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Joint Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Synovitis; Tendinopathy; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular
• Other Study ID Numbers: DCC-3014-03-001; 2024-513624-42-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No