Clinical trial NCT05059262: Study of Vimseltinib for Tenosynovial Giant Cell Tumor
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Tenosynovial Giant Cell Tumor
Pigmented Villonodular Synovitis
Giant Cell Tumor of Tendon Sheath
Tenosynovial Giant Cell Tumor, Diffuse
Tenosynovial Giant Cell Tumor, Localized
Keywords: TGCT
PVNS
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2021-09-28
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) at Week 25 Per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
Secondary outcomes:
measure: ORR at Week 25 Per Tumor Volume Score (TVS)
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Change From Baseline in Active Range of Motion (ROM) at Week 25
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 25
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Change From Baseline in the Worst Stiffness Numeric Rating Scale (NRS) Score at Week 25
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Change From Baseline in EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Percentage of Participants With Response at Week 25 Based on Brief Pain Inventory (BPI) Worst Pain NRS Score and Narcotic Analgesic Use
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Sarcoma Research
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: Montréal
country: Canada
facility: McGill University
city: Toronto
country: Canada
facility: Princess Margaret Hospital
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre Léon Bérard
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Essen
country: Germany
facility: University Hospital Essen (Universitätsklinikum Essen)
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Naples
country: Italy
facility: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
city: Padua
country: Italy
facility: Istituto Oncologico Veneto
city: Rome
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Warsaw
country: Poland
facility: Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Basel
country: Switzerland
facility: Universitäts-Kinderspital beider Basel (UKBB)
city: London
country: United Kingdom
facility: Cancer & Haematology Centre, The Churchill Hospital - Oxford University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals
Study officials:
References: