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

ClinicalTrials.gov processed this data on July 25, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

RECRUITING (See Contacts and Locations)
Verified July 2024 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 13, 2022
First Posted: February 3, 2023
Last Update Posted: July 26, 2024
Last Verified: July 2024
History of Changes

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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 Disease Intervention/Treatment
  • Soft Tissue Sarcoma
  • Drug: ADI PEG20
  • Other: Placebo

Study Design

Study TypeInterventional
Anticipated 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 29, 2023
Anticipated Primary Completion DateDecember 30, 2027
Anticipated Study Completion DateDecember 30, 2027

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

    Outcome Measures

    Primary Outcome Measures

    1. Primary End Point of PFS [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)

    Secondary Outcome Measures

    1. 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).]
      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) [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.
    3. 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).]
      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 18 Years to 99 Years (Adult, Older Adult)
    Sexes Eligible for Study All
    Accepts Healthy Volunteers No
    Inclusion Criteria
    • 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.
    • 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).
    • Serum uric acid ≤ 8 mg/dL (with or without medication control).
    • QTc interval range from 350 to 450 ms for adult men and from 360 to 460 ms for adult women.
    • 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.
    • Ability to understand and willingness to sign the informed consent form.
    • 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:
    • 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 other investigational agents.
    • 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.
    • 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 on combination antiretroviral therapy because of the potential for pharmacokinetic interactions 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.

    Contacts and Locations

    Sponsors and Collaborators Polaris Group
    Locations
    • University of Colorado Cancer Center/ CU Anschutz Medical Campus | Aurora, Colorado, United States, 80045
    • University of Miami/ Sylvester Comprehensive Cancer Center | Miami, Florida, United States, 33136
    • Moffitt Cancer Center | Tampa, Florida, United States, 33612
    • Northwestern | Chicago, Illinois, United States, 60611
    • Indiana University | Indianapolis, Indiana, United States, 46202
    • University of Iowa | Iowa City, Iowa, United States, 52242
    • University of Michigan | Ann Arbor, Michigan, United States, 48109
    • Washington University School of Medicine - Siteman Cancer Center | Saint Louis, Missouri, United States, 63110
    • Memorial Sloan Kettering Cancer Center | New York, New York, United States, 10065
    • Duke Cancer Institute | Durham, North Carolina, United States, 27710
    • Wake Forest Baptist (Atrium Health) | Salem, North Carolina, United States, 27157
    • University Hospitals Cleveland Medical Center | Cleveland, Ohio, United States, 44106
    • Ohio State University Wexner Medical Center/ The James Cancer Hospital and Solove Research Institute | Columbus, Ohio, United States, 43210
    • UPenn (Abramson Cancer Center, Pennsylvania Hospital) | Philadelphia, Pennsylvania, United States, 19106
    • University of Texas MD Anderson Cancer Center | Houston, Texas, United States, 77030
    • Medical College of Wisconsin/ Froedtert Hospital | Milwaukee, Wisconsin, United States, 53226
    • UHN - Princess Margaret Cancer Center (Ontario) | Toronto, Ontario, Canada, M5G 2M9
    • McGill University Health Centre (Quebec) | Montréal, Quebec, Canada, H4A 311
    • Chang Gung Medical Foundation Kaohsiung | Kaohsiung City, Niaosong District, Taiwan, 83301
    • National Taiwan University Hospital | Taipei, Taiwan, 10002
    • Taipei Veterans General Hospital | Taipei, Taiwan, 11217
    Investigators

      More Information

      Additional Relevant MeSH Terms

      • Sarcoma
      • Leiomyosarcoma
      • Neoplasms, Connective and Soft Tissue
      • Neoplasms by Histologic Type
      • Neoplasms
      • Neoplasms, Muscle Tissue