Study of Vimseltinib for Tenosynovial Giant Cell Tumor

Tenosynovial Giant Cell Tumor Clinical Trial

— MOTION  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05059262
• Other study ID #: DCC-3014-03-001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 14, 2021
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Deciphera Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: July 2026
• Est. primary completion date: August 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Neoplasms
• Pigmented Villonodular Synovitis
• Synovitis
• Synovitis, Pigmented Villonodular
• Tenosynovial Giant Cell Tumor
• Tenosynovial Giant Cell Tumor, Diffuse

Intervention

Drug:
• vimseltinib
CSF1R inhibitor
• Placebo
Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Deciphera Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Hong Kong,  Italy,  Netherlands,  Norway,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)