Clinical trial NCT05417789: Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)
Official title: A Phase III, Multicentre, Randomised, Double-Blind Study to Assess the Safety and Efficacy of Emactuzumab vs. Placebo in Subjects With Tenosynovial Giant Cell Tumour
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: TGCT
Keywords: TGCT, Tenosynovial Giant Cell Tumour
PVNS, Pigmented Villonodular Synovitis
Synovitis
Emactuzumab
Local TGCT
Diffuse TGCT
Lead sponsor: SynOx Therapeutics Limited
Sponsor class: INDUSTRY
First posted: 2022-06-14
Enrollment: 128
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, Phase 3, randomised, double-blind, placebo-controlled study, which aims to evaluate the efficacy and safety of the investigational drug emactuzumab for the treatment of patients with localized or diffuse TGCT where surgical removal of the tumor is not viewed as an option.

The study consists of two parts. In Part 1, eligible subjects will be assigned in a 2:1 ratio to receive either emactuzumab or matching placebo in a double-blind fashion, that will be administered in total 5 times as an intravenous (i.v.) infusion once every 2 weeks. This will be followed by an observation period of 3 months leading to a total duration of 24 weeks in Part 1. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. Part 2 is a long-term double-blind follow-up phase of the subjects on emactuzumab or placebo. Subjects assigned to placebo in Part 1 have the option, subject to eligibility, to crossover to receive open-label emactuzumab in Part 2. Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment under certain circumstances.


Eligibility criteria: Inclusion Criteria:

* Age \>12 years
* Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where surgical resection would be associated with predicted worsening functional limitations through surgical joint damage, and/or subject has an anticipated high risk of early recurrence as determined by a multidisciplinary tumour board or equivalent, or any other morbidity associated with the surgery, and/or surgical treatment is not expected to improve the clinical outcomes of the subject.
* Measurable disease: longest diameter ≥20 mm.
* Adequate organ and bone marrow function
* If a woman of childbearing potential (WOCBP), must have a negative pregnancy test prior to starting treatment and agree to use a highly effective method of contraception
* Participants must have given written consent

Exclusion Criteria:

* If a female, the subject is pregnant or breast feeding.
* Medical conditions, including auto-immune, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study.
* Known metastatic TGCT or other active cancer that requires concurrent or planned treatment
* Received systemic therapy for TGCT (investigational or approved) targeting CSF-1 or CSF-1R or any multi-tyrosine kinase inhibitor (eg nilotinib and imatinib) within 3 months prior to screening
* Any surgery, chemotherapy or radiotherapy within 3 months of screening
* Unresolved clinically significant toxicity from a previous treatment or any history of serious liver toxicity.
* Current or chronic history of liver disease.
* Inadequate renal and liver function
* Systemic antiretroviral therapy within 3 months of baseline
* Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994) including severe thromboembolic event; incompletely healed clinically significant wounds, including bone fractures; pathological fracture or significant hypercalcaemia.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Day 0 - Day 180 (6 months)
Secondary outcomes:
measure: Physical Function
timeFrame: up to 24 months
measure: Range of Motion (ROM)
timeFrame: up to 24 months
measure: Worst Stiffness
timeFrame: up to 24 months
measure: Worst Pain
timeFrame: up to 24 months
measure: Quality of Life (QoL)
timeFrame: up to 24 months
measure: Duration of response (DoR)
timeFrame: up to 24 months
measure: Tumour volume score (TVS)
timeFrame: up to 24 months
measure: Surgical Intervention Rate
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: NextGen Oncology
state: California
city: Los Angeles
country: United States
facility: Sarcoma Oncology Research Center, LLC
state: California
city: Overland Park
country: United States
facility: University of Kansas Cancer Center (Overland Park) - USOR
state: Kansas
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: OHSU Knight Cancer Institute Hematology Oncology
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Georgetown
country: United States
facility: MedStar Washington Hospital Center
state: Washington
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Brussels
city: Gent
country: Belgium
facility: UZ Gent - Department of Medical Oncology
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Nice
country: France
facility: Centre Antoine Lacassagne
state: Alpes-Maritimes
city: Bordeaux
country: France
facility: Institut Bergonie - PPDS
state: Gironde
city: Saint-Herblain
country: France
facility: Institut de Cancerologie de Ouest - Saint Herblain
state: Loire-Atlantique
city: Lyon
country: France
facility: Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
state: Rhône
city: Lille
country: France
facility: UNICANCER - Centre Oscar Lambret
city: Paris
country: France
facility: AP-HP - Hôpital Cochin - Port-Royal, site Cochin
city: Paris
country: France
facility: Institut Curie - Hôpital de Paris
city: Toulouse
country: France
facility: Oncopole Claudius Regaud Oncologie Médicale
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Campus Bio-Medico
state: Lazio
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia (IRCCS)
state: Piemonte
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
state: Sicily
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
state: Toscana
city: Prato
country: Italy
facility: Nuovo Ospedale di Prato
state: Toscana
city: Bologna
country: Italy
facility: IRCCS lstituto Ortopedico Rizzoli
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
state: Madrin
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Zaragoza
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus Lund
state: Skane lan
city: Basel
country: Switzerland
facility: Universitäts Kinderspital Beider Basel (UKBB)
city: Bern
country: Switzerland
facility: Inselspital - Universitätsspital Bern
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Cancer Haematology Center
Study officials:
affiliation: Comprehensive Cancer Centre of Lyon
name: Jean Y Blay, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: