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

Phase 2

Terminated

Conditions: Leiomyosarcoma

Interventions: Drug: Unesbulin
Other: Placebo
Drug: Dacarbazine

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: 359

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.

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 (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1	Up to approximately 2 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to approximately 2 years	Overall survival was defined as the time in months from the randomization date to the date of death from any cause or date last known alive for those who did not die.
Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1	Up to approximately 2 years	ORR was defined as percentage of participants who achieved a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1	Up to approximately 2 years	DCR was defined as percentage of participants who achieved a confirmed BOR of CR, PR, or at least 3 months of stable disease (SD). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Duration of Response Per Independent Central Review Using RECIST V1.1	Up to approximately 2 years	Duration of response was defined as the time from the date of first confirmed response of CR or PR to the date of the first documented disease progression or death due to any cause, whichever occurred first. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression: 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 mm. The appearance of one or more new lesions was also considered progression.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From first dose of study drug up to approximately 2 years	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A TEAE was defined as an AE that had an onset date on or after the first dose of study drug until 30 days after last dose or occurred prior to first dose of study drug and worsened in severity after first dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Trial Locations

Locations (54): 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
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City of Hope
🇺🇸Duarte, California, United States