Study of ADI-PEG 20 or Placebo Plus Gem and Doc in Previously Treated Subjects With Leiomyosarcoma (ARGSARC)

NCT05712694 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: POLARIS2022-001
• Study Type: interventional
• Target: 300
• Locations: 3 countries
• Sites: 31

Brief Summary

To compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.

Conditions

Soft Tissue Sarcoma

Keywords

Soft Tissue Sarcoma; Arginine; Arginine Deiminase; ADI-PEG 20; Pegargiminase; Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Primary End Point of PFS

  The primary objective is to compare the primary endpoint of PFS in subjects treated with the arginine degrading enzyme ADI-PEG 20 plus Gem and Doc (ADIGemDoc) or PBO plus Gem and Doc (PBOGemDoc) in the 2nd or 3rd line setting using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by blinded independent central review committee (BICR)

  Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years).

Secondary Outcomes (3)

• Secondary End Point of ORR (CR+PR)

  Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years).

• Secondary End Point of Overall Survival (OS)

  Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years).

• Secondary End Point of Safety and Tolerability

  Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years).

Study Arms (2)

ADIGemDoc

EXPERIMENTAL

ADI-PEG 20: 36 mg/m2 on Day -7 of Cycle 1, and Days 1, 8, and 15 of each 21-day cycle Gemcitabine: 600 mg/m2 on days 1 and 8 of each 21-day cycle Docetaxel: 60 mg/m2 on day 8 of each 21-day cycle

Drug: ADI PEG20

PBOGemDoc

PLACEBO COMPARATOR

Placebo: matched PBO on Day -7 of Cycle 1, and Days 1, 8, and 15 of each 21-day cycle Gemcitabine: 900 mg/m2 on days 1 and 8 of each 21-day cycle Docetaxel: 75 mg/m2 on day 8 of each 21-day cycle

Other: Placebo

Interventions

ADI PEG20 DRUG

Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)

Also known as: Pegargiminase

ADIGemDoc

Placebo OTHER

Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)

PBOGemDoc

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject will be eligible for study participation if he/she meets the following criteria:
• Histologically or cytologically confirmed, grade 2 or 3, LMS STS that would be standardly treated with Gem or GemDoc.
• Determination of LMS subtype: uterine or non-uterine.
• Measurable disease per RECIST 1.1 (Appendix A), defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Previous treatment with up to 2 systemic regimens, including at least 1 systemic regimen containing doxorubicin.
• Treatment \> one year ago in the adjuvant/neoadjuvant setting with Gem or Doc is allowed.
• Age \>18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of \< 1 at enrollment (Appendix B).
• Leukocytes ≥ 3,000/mcL.
• Absolute neutrophil count ≥ 1,500/mcL.
• Platelets ≥ 100,000/mcL.
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 2 x ULN. (≤ 3 x ULN for potential subjects with Gilbert's Disease)
• AST(SGOT)/ALT(SGPT) ≤ 3 x ULN (or ≤ 5 x ULN if liver metastases are present)
• Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault equation).

You may not qualify if:

• Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the Investigator will not affect subject outcome in the setting of current diagnosis.
• Currently receiving chemotherapy, immunotherapy, interferon, radiation therapy or other investigational agents. Note: Chemotherapy agent washout period is 5 half-lives prior to randomization. Radiation washout period is 7 days prior to randomization.
• Prior treatment with ADI-PEG 20, Gem or Doc. Patients treated \> one year ago in the adjuvant/neoadjuvant setting with Gem or Doc are allowed to be enrolled.
• Prior pelvic radiation.
• Known brain metastases. Such patients must be excluded from this trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, Gem, Doc, polysorbate 80, pegylated compounds, or other agents used in this study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of seizure disorder not related to underlying cancer.
• Grade 2 or higher neuropathy.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• Known HIV-positivity. Because of the potential for pharmacokinetic interactions of antiretroviral therapy with the study treatment. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Currently receiving other immunosuppressive agents.
• Subjects under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (31)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

USC Norris comprehensive cancer center

Los Angeles, California, 90033, United States

RECRUITING

Stanford University Medical Centre

Palo Alto, California, 94304, United States

RECRUITING

UCSF

San Francisco, California, 94158, United States

RECRUITING

UCLA

Santa Monica, California, 90404, United States

RECRUITING

University of Colorado Cancer Center/ CU Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami/ Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern

Chicago, Illinois, 60611, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

Mass General Brigham Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Ohio State University Wexner Medical Center/ The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

UPenn (Abramson Cancer Center, Pennsylvania Hospital)

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Medical College of Wisconsin/ Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

RECRUITING

UHN - Princess Margaret Cancer Center (Ontario)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

McGill University Health Centre (Quebec)

Montreal, Quebec, H4A 311, Canada

RECRUITING

Chang Gung Medical Foundation Kaohsiung

Kaohsiung City, Niaosong District, 83301, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taipei, 10002, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Taipei, 11217, Taiwan

RECRUITING

MeSH Terms

Conditions

Sarcoma; Leiomyosarcoma

Interventions

ADI PEG20

Condition Hierarchy (Ancestors)

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

Study Officials

• John S Bomalaski

  Polaris Group

  STUDY DIRECTOR

Central Study Contacts

Mirla Langlois

CONTACT

858-452-6688; mlanglois@polarispharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that will compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: February 3, 2023
• Study Start: November 29, 2023
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (26); CA (2); TW (3)