Clinical trial NCT05269355: A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS)
Official title: A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Leiomyosarcoma
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-03-08
Enrollment: 359
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: This study will compare the efficacy and safety of unesbulin plus dacarbazine versus placebo plus dacarbazine in participants with unresectable or metastatic, relapsed or refractory LMS who have received at least 1 prior line of systemic therapy.


Eligibility criteria: Key Inclusion Criteria:

* Histological or cytological confirmation of LMS arising at any anatomic site except bone sarcoma, unresectable or metastatic, relapsed or refractory disease measurable per RECIST 1.1 criteria
* Disease progression on previous treatment before screening or intolerability to other oncology treatments
* Participants with liver metastases may be enrolled
* Participants with well-controlled asthma or chronic obstructive pulmonary disease may be enrolled.
* Toxicity from prior therapies recovered to Grade ≤1 or participant's baseline, except for alopecia. In addition, endocrinopathies associated with prior immunotherapy-based treatments that are well controlled on replacement medication are not exclusionary.
* At least 1 prior systemic cytotoxic or targeted therapy regimen for LMS, which may include but is not limited to single-agent doxorubicin or other anthracycline, doxorubicin plus ifosfamide, trabectedin, pazopanib, or gemcitabine with or without docetaxel.
* At least 4 weeks since prior surgery and recovered in the opinion of investigator

Key Exclusion Criteria:

* Received temozolomide or dacarbazine at any time
* Any other systemic anticancer therapy including investigational agents ≤3 weeks before initiation of study treatment. Additionally, participants may not have received radiation ≤3 weeks before initiation of study treatment.
* Known intolerance to dacarbazine or one or more of the excipients in unesbulin.
* Co-existing active infection or any co-existing medical condition likely to interfere with study procedures
* Gastrointestinal disease or other conditions that could affect absorption. Active peptic ulcer disease, active gastritis, or previous history of gastric perforation within the last 2 years
* Major surgery, open biopsy, or significant traumatic injury that has not recovered, in the opinion of the investigator, within 28 days of baseline
* Immunization with a live vaccine within 30 days before starting study drug due to the risk of serious and life-threatening infections.
* Prior malignancies, other than LMS, that required treatment or have shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ, prostate cancer in situ or any other low risk malignancy that is approved by the medical monitor) during the 5 years before initiation.
* Prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results.

Note: Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to approximately 2 years
measure: Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1
timeFrame: Up to approximately 2 years
measure: Duration of Response Per Independent Central Review Using RECIST V1.1
timeFrame: Up to approximately 2 years
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to approximately 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: University of Florida (UF) Health Cancer Center - Orlando Health
state: Florida
city: Tampa
country: United States
facility: Moffitt
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine - Warrenville Cancer Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Group
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: The Trustees of Columbia University
state: New York
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University (OSU)
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: Barretos
country: Brazil
facility: Fundacao PIO XII - Hospital de Amor
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: INCA I - Instituto Nacional de Cancer
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - Instituto D'Or da Bahia
city: São José do Rio Preto
country: Brazil
facility: CIP - Centro Integrado de Pesquisas do Hospital de Base de Sao Jose do Rio Preto
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de São Paulo (ICESP)
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)
state: Quebec
city: Bordeaux Cedex
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: Institut Curie
city: Villejuif cedex
country: France
facility: Gustave Roussy
city: Mannheim
country: Germany
facility: Universitaetsmedizin Mannheim
city: Munchen
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet Muenchen
city: Budapest
country: Hungary
facility: Eszak-Pesti Centrumkorhaz - Honvedkorhaz
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Torino
country: Italy
facility: La Fondazione e l'Istituto di Candiolo
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Poznan
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Zespól Poradni Specjalistycznych "TERMEDICA"
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia (Hospital Duran y Reynals)
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Glasgow
country: United Kingdom
facility: Beatson, West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: PTC Therapeutics
name: Mark Rance, MD
role: STUDY_DIRECTOR
References: