Clinical trial NCT05804045: Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)
Official title: A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study of ABSK021 to Assess the Efficacy and Safety in Patients With Tenosynovial Giant Cell Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Tenosynovial Giant Cell Tumor
Pigmented Villonodular Synovitis
Giant Cell Tumor of Tendon Sheath
Lead sponsor: Abbisko Therapeutics Co, Ltd
Sponsor class: INDUSTRY
First posted: 2023-04-07
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to assess the efficacy and safety of Pimicotinib (ABSK021) in patients with Tenosynovial Giant Cell Tumor (TGCT). The main questions it aims to answer are:

* Whether the Pimicotinib(ABSK021) works well in patients with TGCT.
* Whether the Pimicotinib(ABSK021) is safe in patients with TGCT.

Participants will be asked to complete the study procedures:

* Receive the administration of Pimicotinib(ABSK021) or placebo (a placebo is a look-alike substance that contains no active drug) about 24 weeks in study part 1.
* Receive the administration of Pimicotinib(ABSK021) about 24 weeks in study part 2.
* Receive the administration of Pimicotinib(ABSK021) till study end in study part 3.
* Complete the study procedures speficied in the protocol, which is guided by researchers.

Detailed description: This study consists of part 1 and part 2. Part 1 is a double-blind phase, eligible patients will be randomized to Pimicotinib(ABSK021) treatment group or matching placebo group and will receive Pimicotinib(ABSK021) or matching placebo until completion of Part 1.

Part 2 is an open-label treatment phase, and all patients entering this phase will receive open-label Pimicotinib(ABSK021) until completion of 24 weeks of dosing or withdrawal from the study.

Part 3 is an open-label extension treatment phase, and patients who completed the part 2 and continuted to be eligible, will go to the Part 3. Patients will receive the open-label Pimicotinib(ABSK021) until all patients withdraw from the study, or the sponsor decides to terminate the study, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

* Patients should understand the study procedures and sign the informed consent form prior to screening.
* Age ≥ 18 years.
* A histologically confirmed TGCT with unresectable.
* Measurable disease as defined by RECIST 1.1, and with at least one lesion of ≥ 2 cm.
* Stable prescription of analgesic regimen for patients with an analgesic need.
* Participants should complete stiffness and pain scales during the screening period, and symptomatic disease because of active TGCT should meet minimum requirements as outlined in study protocol.
* ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1.
* Adequate organ function and bone marrow function.

Exclusion Criteria:

* Known allergy or hypersensitivity to any components of the investigational drug product.
* Previous treatment with highly selective inhibitors targeting CSF-1/CSF-1R. Previous therapy with imatinib and nilotinib is allowed.
* Known additional malignancy that required active treatment and may affect the patient's participation in the study or affect the outcome of the study as assessed by the Investigator.
* Known metastatic TGCT.
* Significant concomitant arthropathy in the affected joint, serious disease, uncontrolled infection.
* Known MRI contraindications.
* Has factors that significantly affected the absorption of oral drug.
* Major surgery or previous anti-tumor therapy for TGCT within 4 weeks prior to randomization.
* Concomitant use of strong CYP inhibitors or inducers as outlined in study protocol.
* Impaired cardiac function or clinically significant cardiac disease.
* Known active human immunodeficiency virus, active hepatitis B, active hepatitis C, or known active tuberculosis.
* Known active liver or biliary disease, or other diseases that may lead to abnormal liver function test results during the study.
* Pregnant or lactating women.
* Childbearing potential males or non-surgically sterilized female patients must agree to use effective methods of contraception during the study.
* Any other clinically significant comorbidities, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline to Week 25
Secondary outcomes:
measure: Objective Response Rate (ORR) per Tumor Volume Score (TVS)
timeFrame: Baseline to Week 25
measure: Range of Motion (ROM)
timeFrame: Baseline to Week 25
measure: Worst Stiffness
timeFrame: Baseline to Week 25
measure: Worst Pain
timeFrame: Baseline to Week 25
measure: Physical Function
timeFrame: Baseline to Week 25
measure: Quality of life (QoL)
timeFrame: Baseline to Week 25
measure: Duration of Response (DOR)
timeFrame: The time (months) from the first documentation of objective response to the first documentation of radiographic disease progression (PD) or death due to any cause, whichever occurs first, assessed up to 24 months.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology
state: California
city: Durham
country: United States
facility: Duke University Medical Center
state: California
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Montréal
country: Canada
facility: McGill University Health Center
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Enshi
country: China
facility: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower hospital
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital&Institute
state: Liaoning
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: Xi'an Honghui Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Wuhan
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Jishuitan Hospital
city: Bologna
country: Italy
facility: IRCCS Istituto Ortopedico Rizzoli
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Prato
country: Italy
facility: Ospedale di Prato
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie National Research Institute of Oncology
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
Study officials:
References: