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

NCT ID: NCT05269355

Last Updated: 2025-06-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 359 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-23
• Study Completion Date: 2024-07-17

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.

Conditions

Leiomyosarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Unesbulin and 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.

Group Type: EXPERIMENTAL

Unesbulin

Intervention Type: DRUG

Unesbulin will be administered as per the dose and schedule specified in the arm description.

Dacarbazine

Intervention Type: DRUG

Dacarbazine will be administered as per the dose and schedule specified in the arm description.

Placebo and 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.

Group Type: PLACEBO_COMPARATOR

Dacarbazine

Intervention Type: DRUG

Dacarbazine will be administered as per the dose and schedule specified in the arm description.

Placebo

Intervention Type: OTHER

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

Interventions

Unesbulin

Unesbulin will be administered as per the dose and schedule specified in the arm description.

Intervention Type: DRUG

Dacarbazine

Dacarbazine will be administered as per the dose and schedule specified in the arm description.

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

PTC596; DTIC

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PTC Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Rance, MD

Role: STUDY_DIRECTOR

PTC Therapeutics

Locations

City of Hope

Duarte, California, United States

University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Sarcoma Oncology Research Center

Santa Monica, California, United States

Stanford Cancer Center

Stanford, California, United States

University of Colorado Denver

Denver, Colorado, 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

Moffitt

Tampa, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, 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

St 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

Duke University Medical Center

Durham, North Carolina, United States

The Ohio State University (OSU)

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Chris O'Brien Lifehouse

Camperdown, , Australia

Peter MacCallum Cancer Institute

East Melbourne, , Australia

Prince of Wales Hospital

Randwick, , Australia

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, , Brazil

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)

Montreal, Quebec, Canada

Institut Bergonie

Bordeaux, , France

Centre Leon Berard

Lyon, , France

Institut Curie

Paris, , France

Gustave Roussy

Villejuif, , France

Universitaetsmedizin Mannheim

Mannheim, , Germany

Klinikum der Ludwig-Maximilians-Universitaet Muenchen

München, , Germany

Eszak-Pesti Centrumkorhaz - Honvedkorhaz

Budapest, , Hungary

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

La Fondazione e l'Istituto di Candiolo

Torino, , Italy

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

Warsaw, , Poland

Institut Catala d'Oncologia (Hospital Duran y Reynals)

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

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

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2022-000073-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PTC596-ONC-008-LMS

Identifier Type: -

Identifier Source: org_study_id