A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS)

Leiomyosarcoma Clinical Trial

— SUNRISELMS  

Official title:

A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05269355
• Other study ID #: PTC596-ONC-008-LMS
• Secondary ID: 2022-000073-12
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: May 23, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2024
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leiomyosarcoma

Intervention

Drug:
• Unesbulin
Unesbulin will be administered as per the dose and schedule specified in the arm description.
• Dacarbazine
Dacarbazine will be administered as per the dose and schedule specified in the arm description.

Other:
• Placebo
Placebo will be administered as per the schedule specified in the arm description.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown
Australia	Peter MacCallum Cancer Institute	East Melbourne
Australia	Prince of Wales Hospital	Randwick
Brazil	Fundacao PIO XII - Hospital de Amor	Barretos
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	INCA I - Instituto Nacional de Cancer	Rio de Janeiro
Brazil	Hospital Sao Rafael - Instituto D'Or da Bahia	Salvador
Brazil	CIP - Centro Integrado de Pesquisas do Hospital de Base de Sao Jose do Rio Preto	São José do Rio Preto
Brazil	Instituto do Cancer do Estado de São Paulo (ICESP)	São Paulo
Canada	Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
France	Institut Bergonie	Bordeaux Cedex
France	Centre Leon Berard	Lyon
France	Institut Curie	Paris
France	Gustave Roussy	Villejuif cedex
Germany	Universitaetsmedizin Mannheim	Mannheim
Germany	Klinikum der Ludwig-Maximilians-Universitaet Muenchen	Munchen
Hungary	Eszak-Pesti Centrumkorhaz - Honvedkorhaz	Budapest
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	La Fondazione e l'Istituto di Candiolo	Torino
Netherlands	Leids Universitair Medisch Centrum	Leiden
Poland	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
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Institut Catala d'Oncologia (Hospital Duran y Reynals)	Barcelona
Spain	Hospital Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
United Kingdom	Beatson, West of Scotland Cancer Centre	Glasgow
United Kingdom	Royal Marsden Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins Oncology Group	Baltimore	Maryland
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The Ohio State University (OSU)	Columbus	Ohio
United States	University of Colorado Denver	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York
United States	The Trustees of Columbia University	New York	New York
United States	University of Florida (UF) Health Cancer Center - Orlando Health	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University	Saint Louis	Missouri
United States	Sarcoma Oncology Research Center	Santa Monica	California
United States	Stanford Cancer Center	Stanford	California
United States	Moffitt	Tampa	Florida
United States	Northwestern Medicine - Warrenville Cancer Center	Warrenville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival		From the date of randomization to the date of death due to any cause (up to approximately 2 years)
Secondary	Objective Response Rate (ORR)	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.	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)
Secondary	Disease Control Rate (DCR)	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.	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)
Secondary	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)
Secondary	Number of Participants with Treatment-emergent Adverse Events		From the date of randomization up to approximately 2 years