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

• ClinicalTrials.gov Identifier: NCT05269355
• Recruitment Status: Recruiting
• First Posted: March 8, 2022
• Last Update Posted: May 26, 2023
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

Tracking Information

• First Submitted Date: February 25, 2022
• First Posted Date: March 8, 2022
• Last Update Posted Date: May 26, 2023
• Actual Study Start Date: May 23, 2022
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 25, 2022): Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Assessed by an Independent Central Imaging Laboratory [ Time Frame: 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) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 25, 2022)

• Overall Survival [ Time Frame: From the date of randomization to the date of death due to any cause (up to approximately 2 years) ]
• Objective Response Rate (ORR) [ Time Frame: 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.
• Disease Control Rate (DCR) [ Time Frame: 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 stable disease (≥3 months) using RECIST 1.1 as per independent radiologist assessment.
• Duration of Response per RECIST 1.1 Assessed by an Independent Central Imaging Laboratory [ Time Frame: 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) ]
• Number of Participants with Treatment-emergent Adverse Events [ Time Frame: From the date of randomization up to approximately 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS)
• Official Title: A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Leiomyosarcoma

Intervention

• Drug: Unesbulin
  Unesbulin will be administered as per the dose and schedule specified in the arm description.
  Other Name: PTC596
• Drug: Dacarbazine
  Dacarbazine will be administered as per the dose and schedule specified in the arm description.
  Other Name: DTIC
• Other: Placebo
  Placebo will be administered as per the schedule specified in the arm description.

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: Unesbulin
  • Drug: Dacarbazine
• Placebo Comparator: 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.
  Interventions:

  • Drug: Dacarbazine
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 25, 2022): 345
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
• 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 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
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Patient Advocacy; 1-866-562-4620; medinfo@ptcbio.com

• Listed Location Countries: Australia, Brazil, Canada, France, Hungary, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05269355
• Other Study ID Numbers: PTC596-ONC-008-LMS
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: PTC Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: PTC Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Mark Rance, MD; PTC Therapeutics

• PRS Account: PTC Therapeutics
• Verification Date: May 2023