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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by Polaris Group
Sponsor
Polaris Group
Information Provided by (Responsible Party)
Polaris Group
Clinicaltrials.gov Identifier
NCT05712694
Other Study ID Numbers:
POLARIS2022-001
First Submitted
December 12, 2022
First Posted
February 2, 2023
Last Update Posted
April 19, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Soft Tissue Sarcoma
Drug: ADI PEG20Other: Placebo

Study Design

Study TypeInterventional
Actual Enrollment300 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleADI-PEG 20 or Placebo Plus Gemcitabine and Docetaxel in Previously Treated Subjects With Leiomyosarcoma (ARGSARC): A Randomized, Double Blind, Multi-Center Phase 3 Trial
Study Start DateNovember 28, 2023
Actual Primary Completion Date1yr 7mos from now
Actual Study Completion Date1yr 7mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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)
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)

Outcome Measures

Primary Outcome Measures
  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)
Secondary Outcome Measures
  1. Secondary End Point of ORR (CR+PR)
    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.
  2. Secondary End Point of Overall Survival (OS)
    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.
  3. Secondary End Point of Safety and Tolerability
    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).

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsPolaris Group
Locations
Mayo Clinic Arizona | Phoenix Arizona, United States, 85054USC Norris comprehensive cancer center | Los Angeles California, United States, 90033Stanford University Medical Centre | Palo Alto California, United States, 94304UCSF | San Francisco California, United States, 94158UCLA | Santa Monica California, United States, 90404University of Colorado Cancer Center/ CU Anschutz Medical Campus | Aurora Colorado, United States, 80045Mayo Clinic Florida | Jacksonville Florida, United States, 32224University of Miami/ Sylvester Comprehensive Cancer Center | Miami Florida, United States, 33136Moffitt Cancer Center | Tampa Florida, United States, 33612Northwestern | Chicago Illinois, United States, 60611Indiana University | Indianapolis Indiana, United States, 46202University of Iowa | Iowa City Iowa, United States, 52242Mass General Brigham Cancer Center | Boston Massachusetts, United States, 02114University of Michigan | Ann Arbor Michigan, United States, 48109Mayo Clinic Rochester | Rochester Minnesota, United States, 55905Washington University School of Medicine - Siteman Cancer Center | St Louis Missouri, United States, 63110NYU Langone Health | New York New York, United States, 10016Columbia University | New York New York, United States, 10032Memorial Sloan Kettering Cancer Center | New York New York, United States, 10065Duke Cancer Institute | Durham North Carolina, United States, 27710University Hospitals Cleveland Medical Center | Cleveland Ohio, United States, 44106Ohio State University Wexner Medical Center/ The James Cancer Hospital and Solove Research Institute | Columbus Ohio, United States, 43210UPenn (Abramson Cancer Center, Pennsylvania Hospital) | Philadelphia Pennsylvania, United States, 19106UPMC Hillman Cancer Center | Pittsburgh Pennsylvania, United States, 15232University of Texas MD Anderson Cancer Center | Houston Texas, United States, 77030Medical College of Wisconsin/ Froedtert Hospital | Milwaukee Wisconsin, United States, 53226UHN - Princess Margaret Cancer Center (Ontario) | Toronto Ontario, Canada, M5G 2M9McGill University Health Centre (Quebec) | Montreal Quebec, Canada, H4A 311Chang Gung Medical Foundation Kaohsiung | Kaohsiung City Niaosong District, Taiwan, 83301National Taiwan University Hospital | Taipei Taipei, Taiwan, 10002Taipei Veterans General Hospital | Taipei Taipei, Taiwan, 11217
Investigators
Study Director: John S Bomalaski, Polaris Group