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

NCT05269355 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: PTC596-ONC-008-LMS2022-000073-12
• Study Type: interventional
• Target: 359
• Locations: 12 countries
• Sites: 54

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1

  PFS was defined as the time from randomization to the documented disease progression or death due to any cause, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression.

  Up to approximately 2 years

Secondary Outcomes (5)

• Overall Survival

  Up to approximately 2 years

• Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1

  Up to approximately 2 years

• Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1

  Up to approximately 2 years

• Duration of Response Per Independent Central Review Using RECIST V1.1

  Up to approximately 2 years

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  From first dose of study drug up to approximately 2 years

Study Arms (2)

Unesbulin and Dacarbazine

EXPERIMENTAL

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.

Drug: Unesbulin; Drug: Dacarbazine

Placebo and Dacarbazine

PLACEBO COMPARATOR

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.

Drug: Dacarbazine; Other: Placebo

Interventions

Unesbulin DRUG

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

Also known as: PTC596

Unesbulin and Dacarbazine

Dacarbazine DRUG

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

Also known as: DTIC

Placebo and Dacarbazine; Unesbulin and Dacarbazine

Placebo OTHER

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

Placebo and Dacarbazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (54)

City of Hope

Duarte, California, 91010, United States

Location

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

Los Angeles, California, 90024, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University of Florida (UF) Health Cancer Center - Orlando Health

Orlando, Florida, 32806, United States

Location

Moffitt

Tampa, Florida, 33612, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Northwestern Medicine - Warrenville Cancer Center

Warrenville, Illinois, 60555, United States

Location

Johns Hopkins Oncology Group

Baltimore, Maryland, 21231, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

The Trustees of Columbia University

New York, New York, 10027, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 11101, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University (OSU)

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19144, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Chris O'Brien Lifehouse

Camperdown, 2050, Australia

Location

Peter MacCallum Cancer Institute

East Melbourne, 3000, Australia

Location

Prince of Wales Hospital

Randwick, 2031, Australia

Location

Fundacao PIO XII - Hospital de Amor

Barretos, Brazil

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Brazil

Location

INCA I - Instituto Nacional de Cancer

Rio de Janeiro, 20220-410, Brazil

Location

Hospital Sao Rafael - Instituto D'Or da Bahia

Salvador, Brazil

Location

CIP - Centro Integrado de Pesquisas do Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, Brazil

Location

Instituto do Cancer do Estado de São Paulo (ICESP)

São Paulo, Brazil

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)

Montreal, Quebec, Canada

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut Curie

Paris, 75005, France

Location

Gustave Roussy

Villejuif, France

Location

Universitaetsmedizin Mannheim

Mannheim, 68167, Germany

Location

Klinikum der Ludwig-Maximilians-Universitaet Muenchen

München, 81377, Germany

Location

Eszak-Pesti Centrumkorhaz - Honvedkorhaz

Budapest, Hungary

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

La Fondazione e l'Istituto di Candiolo

Torino, 10060, Italy

Location

Leids Universitair Medisch Centrum

Leiden, Netherlands

Location

Niepubliczny Zaklad Opieki Zdrowotnej Zespól Poradni Specjalistycznych "TERMEDICA"

Poznan, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow

Warsaw, 02-781, Poland

Location

Institut Catala d'Oncologia (Hospital Duran y Reynals)

Barcelona, 08908, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Beatson, West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

PTC596; Dacarbazine

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was terminated early due to business decision.

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Mark Rance, MD

  PTC Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2022
• First Posted: March 8, 2022
• Study Start: May 23, 2022
• Primary Completion: June 17, 2024
• Study Completion: July 17, 2024
• Last Updated: June 13, 2025
• Results First Posted: June 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); CA (3); US (23); IT (2); DE (2); AU (3); GB (3); FR (4); HU (1); PL (2); ES (4); BR (6)