A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS)
- Conditions
- Leiomyosarcoma
- Interventions
- Registration Number
- NCT05269355
- Lead Sponsor
- PTC Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 360
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo and Dacarbazine Placebo Participants will receive placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m\^2 IV once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. Unesbulin and Dacarbazine Unesbulin Participants will receive unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/meter squared (m\^2) intravenously (IV) once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. Unesbulin and Dacarbazine Dacarbazine Participants will receive unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/meter squared (m\^2) intravenously (IV) once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. Placebo and Dacarbazine Dacarbazine Participants will receive placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m\^2 IV once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
- Primary Outcome Measures
Name Time Method Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Assessed by an Independent Central Imaging Laboratory From the date of randomization to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 2 years)
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) From the date of randomization until the date of objectively documented progression or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 2 years) ORR is defined as the number of participants who achieve a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST 1.1 as per independent radiologist assessment.
Number of Participants with Treatment-emergent Adverse Events From the date of randomization up to approximately 2 years Disease Control Rate (DCR) From the date of randomization until the date of the first documented tumor progression or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 2 years) DCR is defined as the number of participants with BOR of CR, PR, or at least 3 months of stable disease using RECIST 1.1 as per independent radiologist assessment.
Overall Survival From the date of randomization to the date of death due to any cause (up to approximately 2 years) Duration of Response per RECIST 1.1 Assessed by an Independent Central Imaging Laboratory Time from the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 2 years)
Trial Locations
- Locations (54)
University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
The Ohio State University (OSU)
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Moffitt
🇺🇸Tampa, Florida, United States
University of Colorado Denver
🇺🇸Denver, Colorado, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
City of Hope
🇺🇸Duarte, California, United States
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
University of Florida (UF) Health Cancer Center - Orlando Health
🇺🇸Orlando, Florida, United States
Northwestern Medicine - Warrenville Cancer Center
🇺🇸Warrenville, Illinois, United States
Johns Hopkins Oncology Group
🇺🇸Baltimore, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
The Trustees of Columbia University
🇺🇸New York, New York, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, Australia
Peter MacCallum Cancer Institute
🇦🇺East Melbourne, Australia
Prince of Wales Hospital
🇦🇺Randwick, Australia
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Fundacao PIO XII - Hospital de Amor
🇧🇷Barretos, Brazil
CIP - Centro Integrado de Pesquisas do Hospital de Base de Sao Jose do Rio Preto
🇧🇷São José do Rio Preto, Brazil
INCA I - Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Hospital Sao Rafael - Instituto D'Or da Bahia
🇧🇷Salvador, Brazil
Instituto do Cancer do Estado de São Paulo (ICESP)
🇧🇷São Paulo, Brazil
Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)
🇨🇦Montreal, Quebec, Canada
Institut Bergonie
🇫🇷Bordeaux Cedex, France
Institut Curie
🇫🇷Paris, France
Gustave Roussy
🇫🇷Villejuif cedex, France
Centre Leon Berard
🇫🇷Lyon, France
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
🇩🇪Munchen, Germany
La Fondazione e l'Istituto di Candiolo
🇮🇹Torino, Italy
Eszak-Pesti Centrumkorhaz - Honvedkorhaz
ðŸ‡ðŸ‡ºBudapest, Hungary
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Universitaetsmedizin Mannheim
🇩🇪Mannheim, Germany
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Niepubliczny Zaklad Opieki Zdrowotnej Zespól Poradni Specjalistycznych "TERMEDICA"
🇵🇱Poznan, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
🇵🇱Warszawa, Poland
Institut Catala d'Oncologia (Hospital Duran y Reynals)
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Beatson, West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Royal Marsden Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States