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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05712694
Recruitment Status : Recruiting
First Posted : February 3, 2023
Last Update Posted : May 13, 2024
Sponsor:
Information provided by (Responsible Party):
Polaris Group

Tracking Information
First Submitted Date  ICMJE December 13, 2022
First Posted Date  ICMJE February 3, 2023
Last Update Posted Date May 13, 2024
Actual Study Start Date  ICMJE November 29, 2023
Estimated Primary Completion Date December 30, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2023)		 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2023)
  • 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.
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ADI-PEG 20 or Placebo Plus Gem and Doc in Previously Treated Subjects With Leiomyosarcoma (ARGSARC)
Official Title  ICMJE 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
Brief Summary To compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model 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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial
Primary Purpose: Treatment
Condition  ICMJE Soft Tissue Sarcoma
Intervention  ICMJE
  • Drug: ADI PEG20
    Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)
    Other Name: Pegargiminase
  • Other: Placebo
    Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)
Study Arms  ICMJE
  • 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
    Intervention: Drug: ADI PEG20
  • 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
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2023)		 300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2027
Estimated Primary Completion Date December 30, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Total bilirubin ≤ 2 x ULN. (≤ 3 x ULN for potential subjects with Gilbert's Disease)
    12. AST(SGOT)/ALT(SGPT) ≤ 3 x ULN (or ≤ 5 x ULN if liver metastases are present)
    13. Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault equation).
    14. Serum uric acid ≤ 8 mg/dL (with or without medication control).
    15. QTc interval range from 350 to 450 ms for adult men and from 360 to 460 ms for adult women.
    16. 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.
    17. Ability to understand and willingness to sign the informed consent form.
    18. 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 other investigational agents.
    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. 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.
    5. 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.
    6. 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.
    7. History of seizure disorder not related to underlying cancer.
    8. Grade 2 or higher neuropathy.
    9. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
    10. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mirla Langlois 858-452-6688 ext 161 mlanglois@polarispharma.com
Contact: Stephanie V Rumund 858-452-6688 svanrumund@polarispharma.com
Listed Location Countries  ICMJE Canada,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05712694
Other Study ID Numbers  ICMJE POLARIS2022-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Polaris Group
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Polaris Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: John S Bomalaski Polaris Group
PRS Account Polaris Group
Verification Date December 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP