Clinical trial NCT05712694: Study of ADI-PEG 20 or Placebo Plus Gem and Doc in Previously Treated Subjects With Leiomyosarcoma (ARGSARC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Soft Tissue Sarcoma
Keywords: Soft Tissue Sarcoma
Arginine
Arginine Deiminase
ADI-PEG 20
Pegargiminase
Leiomyosarcoma
Lead sponsor: Polaris Group
Sponsor class: INDUSTRY
First posted: 2023-02-03
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary End Point of PFS
timeFrame: 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:
measure: Secondary End Point of ORR (CR+PR)
timeFrame: 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).
measure: Secondary End Point of Overall Survival (OS)
timeFrame: 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).
measure: Secondary End Point of Safety and Tolerability
timeFrame: 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).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: USC Norris comprehensive cancer center
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center/ CU Anschutz Medical Campus
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: University of Miami/ Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Mass General Brigham Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center/ The James Cancer Hospital and Solove Research Institute
state: Ohio
city: Philadelphia
country: United States
facility: UPenn (Abramson Cancer Center, Pennsylvania Hospital)
state: Pennsylvania
city: Pittsburg
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/ Froedtert Hospital
state: Wisconsin
city: Toronto
country: Canada
facility: UHN - Princess Margaret Cancer Center (Ontario)
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre (Quebec)
state: Quebec
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Medical Foundation Kaohsiung
state: Niaosong District
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Polaris Group
name: John S Bomalaski
role: STUDY_DIRECTOR
References: