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

April 15, 2026 updated by: Polaris Group

ADI-PEG 20 or Placebo Plus Gemcitabine and Docetaxel in Previously Treated Subjects With Leiomyosarcoma (ARGSARC): A Randomized, Double Blind, Multi-Center Phase 3 Trial

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • UHN - Princess Margaret Cancer Center (Ontario)
        • Contact:
        • Principal Investigator:
          • Albiruni Razak, MB BCh
    • Quebec
      • Montreal, Quebec, Canada, H4A 311
        • Recruiting
        • McGill University Health Centre (Quebec)
        • Contact:
        • Principal Investigator:
          • Ramy Saleh, MD
  • Taiwan
    • Niaosong District
      • Kaohsiung City, Niaosong District, Taiwan, 83301
        • Recruiting
        • Chang Gung Medical Foundation Kaohsiung
        • Principal Investigator:
          • Yu-Li Su, MD
        • Contact:
    • Taipei
      • Taipei, Taipei, Taiwan, 10002
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
        • Principal Investigator:
          • Wei-Wu (Tom) Chen, MD
      • Taipei, Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
        • Principal Investigator:
          • Chueh-Chuan Yen
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
        • Principal Investigator:
          • Mahesh Seetharam, MD
        • Contact:
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC Norris Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Mark Agulnik, M.D
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University Medical Centre
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nam Bui, MD
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF
        • Contact:
        • Principal Investigator:
          • Varun Monga, M.D
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA
        • Contact:
        • Principal Investigator:
          • Arun Singh, M.D
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Cancer Center/ CU Anschutz Medical Campus
        • Principal Investigator:
          • Breelyn Wilky, MD
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
        • Contact:
        • Principal Investigator:
          • Steven Attia, DO
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami/ Sylvester Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Emily Jonczak, MD
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Mihaela Druta, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern
        • Principal Investigator:
          • Seth Pollack, MD
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University
        • Contact:
        • Principal Investigator:
          • Samantha Armstrong, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Active, not recruiting
        • University of Iowa
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Mass General Brigham Cancer Center
        • Contact:
        • Principal Investigator:
          • Edwin Choy, M.D
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Rashmi Chugh, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Contact:
        • Principal Investigator:
          • Brittany Siontis, M.D
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine - Siteman Cancer Center
        • Principal Investigator:
          • Brian Van Tine, MD
        • Contact:
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health
        • Principal Investigator:
          • Matthew Ingham, MD
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Viswatej Avutu, MD
        • Contact:
      • New York, New York, United States, 10032
        • Not yet recruiting
        • Columbia University
        • Contact:
        • Principal Investigator:
          • Igor Matushansky, M.D.Ph.D
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke Cancer Institute
        • Contact:
        • Principal Investigator:
          • Juneko Grilley-Olson, MD
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
        • Principal Investigator:
          • Ankit Mangla, MD
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Wexner Medical Center/ The James Cancer Hospital and Solove Research Institute
        • Principal Investigator:
          • David Liebner, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • Recruiting
        • UPenn (Abramson Cancer Center, Pennsylvania Hospital)
        • Principal Investigator:
          • Lee Hartner, MD
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Contact:
        • Principal Investigator:
          • Melissa Burgess, M.D
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • John A Livingston, MD
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin/ Froedtert Hospital
        • Principal Investigator:
          • John Charlson, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • A subject will be eligible for study participation if he/she meets the following criteria:

    1. Histologically or cytologically confirmed, grade 2 or 3, LMS STS that would be standardly treated with Gem or GemDoc.
    2. Determination of LMS subtype: uterine or non-uterine.
    3. 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.
    4. Previous treatment with up to 2 systemic regimens, including at least 1 systemic regimen containing doxorubicin.
    5. Treatment > one year ago in the adjuvant/neoadjuvant setting with Gem or Doc is allowed.
    6. Age >18 years.
    7. Eastern Cooperative Oncology Group (ECOG) performance status of < 1 at enrollment (Appendix B).
    8. Leukocytes ≥ 3,000/mcL.
    9. Absolute neutrophil count ≥ 1,500/mcL.
    10. Platelets ≥ 100,000/mcL.
    11. Hemoglobin ≥ 8.0 g/dL
    12. Total bilirubin ≤ 2 x ULN. (≤ 3 x ULN for potential subjects with Gilbert's Disease)
    13. AST(SGOT)/ALT(SGPT) ≤ 3 x ULN (or ≤ 5 x ULN if liver metastases are present)
    14. Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault equation).
    15. Serum uric acid ≤ 8 mg/dL (with or without medication control).
    16. QTc interval range from 350 to 450 ms for adult men and from 360 to 460 ms for adult women.
    17. Subjects and their partners must be asked to use appropriate contraception. They must agree to use 2 forms of contraception or agree to refrain from intercourse for the duration of the study and for 35 days after the last dose of ADI-PEG 20 or for at least 3 months (male subjects) or 6 months (female subjects) after treatment with gemcitabine, whichever is the longer duration.
    18. Ability to understand and willingness to sign the informed consent form.
    19. No concurrent investigational drug studies are allowed.

Exclusion Criteria:

  • A subject will not be eligible for study participation if he/she meets any of the exclusion criteria:

    1. 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.
    2. 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.
    3. 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.
    4. Prior pelvic radiation.
    5. 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.
    6. 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.
    7. 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.
    8. History of seizure disorder not related to underlying cancer.
    9. Grade 2 or higher neuropathy.
    10. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
    11. 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.
    12. Currently receiving other immunosuppressive agents.
    13. Subjects under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ADIGemDoc
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
Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)
Other Names:
  • Pegargiminase
Placebo Comparator: PBOGemDoc
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
Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary End Point of PFS
Time Frame: 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).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary End Point of ORR (CR+PR)
Time Frame: 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).

The secondary objectives are to compare ADIGemDoc versus PBOGemDoc with respect to:

Objective response rate (ORR) (complete response [CR] + partial response [PR]) The secondary endpoint of ORR will be assessed by BICR using RECIST 1.1 and tested using a CMH test stratified by the stratification factors used during the randomization based on the ITT population.
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)
Time Frame: 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).

The secondary objectives are to compare ADIGemDoc versus PBOGemDoc with respect to:

OS

The secondary endpoint of OS will be tested using a log-rank test stratified by the stratification factors used during the randomization based on the ITT population. A stratified Cox model will be used to estimate HR and 95% CI, and KM curves will be used to estimate OS median and 95% CI.
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
Time Frame: 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).
All clinically significant abnormalities and deteriorations will be followed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE V5).
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Polaris Group

Investigators

  • Study Director: John S Bomalaski, Polaris Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2023

Primary Completion (Estimated)

December 30, 2027

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

December 13, 2022

First Submitted That Met QC Criteria

January 31, 2023

First Posted (Actual)

February 3, 2023

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • POLARIS2022-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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