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 (Estimated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
    • Chris O'Brien Lifehouse
• Canada
  • Montréal, Canada
    • McGill University
  • Toronto, Canada
    • Princess Margaret Hospital
• France
  • Bordeaux, France
    • Institut Bergonie
  • Lyon, France
    • Centre Léon Bérard
  • 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 Clínico 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 CSFR1 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: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1/Part 2 - vimseltinib/vimseltinib; Participants receive blinded treatment of 30 mg twice a week (biw) vimseltinib for 24 weeks in Part 1 and continue on 30 mg biw vimseltinib in Part 2	Drug: vimseltinib; CSF1R inhibitor; Other Names: DCC-3014
Placebo Comparator: Part 1/Part 2 - placebo/vimseltinib; Participants receive blinded treatment of 30 mg twice a week (biw) matching placebo for 24 weeks in Part 1 and have option to receive 30 mg biw vimseltinib in Part 2	Drug: Placebo; Placebo; Drug: vimseltinib; CSF1R inhibitor; Other Names: DCC-3014

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR= complete response [CR]+partial response [PR]) per RECIST Version 1,1	Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1	Baseline to Week 25 (Cycle 7, Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR per Tumor Volume Score (TVS)	Assessed by central read using Tumor Volume Score (TVS). TVS is a semi-quantitative 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.	Baseline to Week 25 (Cycle 7, Day 1)
Range of motion (ROM)	Mean change from baseline in active ROM of the affected joint, relative to a reference standard at Week 25	Baseline to Week 25 (Cycle 7, Day 1)
Physical function	Mean change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25	Baseline to Week 25 (Cycle 7, Day 1)
Worst stiffness	Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score at Week 25	Baseline to Week 25 (Cycle 7, Day 1)
Quality of life (QoL)	Mean change from baseline in EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25	Baseline to Week 25 (Cycle 7, Day 1)
Worst pain	Proportion of responders, with a response defined as 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	Baseline to Week 25 (Cycle 7, Day 1)

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2021
• Primary Completion (Actual): August 10, 2023
• Study Completion (Estimated): July 1, 2026

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): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

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

Drug and device information, study documents

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