A Study of Unesbulin (PTC596) in Combination With Dacarbazine in Participants With Advanced Leiomyosarcoma (LMS)

NCT03761095 | Completed Phase 1 FDA Drug

• 1 other identifier: PTC596-ONC-007-LMS
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of unesbulin in combination with dacarbazine for the treatment of advanced LMS and determine the overall safety profile of unesbulin in combination with dacarbazine. This study will employ the time-to-event continual reassessment method (TITE-CRM) for dose finding. Treatment will be initiated at dose level 2 (DL2) (Dacarbazine 1000 milligrams per square meter \[mg/m\^2\] intravenously \[IV\] every 21 days in combination with unesbulin 200 milligrams \[mg\] orally twice weekly) for the first participant. This dose level represents the investigator's best assessment of the MTD based on available toxicity data for both agents. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose-limiting toxicity (DLT) information from all participants previously treated. To enroll additional participants at the RP2D, the study is amended to include an expansion cohort of up to 12 participants (some of whom could be ongoing participants who reconsent). Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

Conditions

Leiomyosarcoma

Outcome Measures

Primary Outcomes (2)

• MTD and RP2D of Unesbulin in Combination With Dacarbazine

  MTD will be determined using the TITE-CRM for dose-finding. MTD is defined as the dose associated with a target probability of DLT of 0.25.

  First 2 cycles of treatment (6 weeks)

• Number of Participants With Adverse Events

  From screening until end of study (up to approximately 1.5 years)

Secondary Outcomes (13)

• Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  From Baseline until the date of objectively documented progression per RECIST v1.1 or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 1.5 years)

• Time to Response as Determined by the Investigator Using RECIST v1.1

  From Baseline until the date of first occurrence of CR or PR (up to approximately 1.5 years)

• Duration of Response (DOR)

  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 1.5 years)

• Progression-Free Survival (PFS)

  Time from the first dose of study drug to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 1.5 years)

• Best Overall Response Rate (Disease Control Rate) (Percentage of Participants With Best Overall Response)

  From Baseline until the date of objectively documented progression per RECIST v1.1 or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 1.5 years)

Study Arms (1)

Unesbulin and Dacarbazine

EXPERIMENTAL

Participants will receive unesbulin orally twice weekly in combination with dacarbazine IV once every 21 days. The first participant will receive dacarbazine 1000 mg/m\^2 IV every 21 days in combination with unesbulin 200 mg tablet orally twice weekly. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose DLT information from all participants previously treated. Participants will receive unesbulin 300 mg twice weekly in combination with dacarbazine in the expansion cohort. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

Drug: Unesbulin; Drug: Dacarbazine

Interventions

Unesbulin DRUG

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

Also known as: PTC596

Unesbulin and Dacarbazine

Dacarbazine DRUG

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

Also known as: DTIC

Unesbulin and Dacarbazine

Eligibility Criteria

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

You may qualify if:

• Signed consent of an Institutional Review Board (IRB)-approved informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (if appropriate).
• Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Disease Status including all of the following:
• Histological or cytological confirmation of LMS arising at any anatomic site.
• Advanced (metastatic) or locally advanced unresectable disease.
• Ineligible for other high-priority national or institutional study.
• Measurable disease per RECIST v1.1 criteria.
• Demographics:
• Age greater than or equal to (\>/=) 18
• Male and Female
• Performance Status:
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Hematopoietic:
• Absolute neutrophil count (ANC) count \>/= 1,500/cubic millimeters (mm\^3) without the use of growth factors in the past 7 days;
• Platelet count \>=100,000/mm\^3 without platelet transfusion in the past 5 days;

You may not qualify if:

• Participants meeting any of the following criteria will not be eligible for enrollment:
• Received any systemic anticancer therapy including investigational agents \<=3 weeks prior to initiation of study treatment. Additionally, Participants may have not received radiation \</= 3 weeks prior to initiation of study treatment.
• Co-existing active infection or any co-existing medical condition likely to interfere with study procedures, including:
• a. Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on electrocardiogram (ECG), marked baseline prolongation of QT/QTc (corrected QT interval) interval, for example, repeated demonstration of a QTc interval \>500 milliseconds (msec) (Long QT Syndrome \[congenital\]).
• Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) positivity.
• History of solid organ transplantation.
• Therapeutics:
• Known or suspected allergy or immediate or delayed hypersensitivity to unesbulin or dacarbazine or any agent given in this study.
• Gastrointestinal:
• Bowel obstruction, malabsorption, or other contraindication to oral medication.
• Gastrointestinal disease or other condition that could affect absorption.
• Active peptic ulcer disease.
• Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis.
• Any condition that impairs participant's ability to swallow oral medications.
• Wounds /Surgery:

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (4)

Mayo Clinic Florida

Jacksonville, Florida, 32204, United States

Location

John Hopkins

Baltimore, Maryland, 21287, United States

Location

Washington University Medical Campus

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Van Tine BA, Ingham MA, Attia S, Meyer CF, Baird JD, Brooks-Asplund E, D'Silva D, Kong R, Mwatha A, O'Keefe K, Weetall M, Spiegel R, Schwartz GK. Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine for the Treatment of Locally Recurrent, Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma. J Clin Oncol. 2024 Jul 10;42(20):2404-2414. doi: 10.1200/JCO.23.01684. Epub 2024 Apr 29.

  PMID: 38684039 DERIVED

Related Links

• Related Info

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 3, 2018
• Study Start: March 13, 2019
• Primary Completion: February 5, 2024
• Study Completion: February 5, 2024
• Last Updated: March 15, 2024

Record last verified: 2024-02

Locations

US (4)