IRB Study Number 24-660
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
To compare 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 Objectives
To compare ADIGemDoc versus PBOGemDoc with respect to:
Objective response rate (ORR) (complete response [CR] + partial response [PR])
• Overall survival (OS)
• Safety and tolerability
Inclusion 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.
Prior treatment with up to 2 systemic regimens for advanced/metastatic LMS; previous exposure to an anthracycline at any time.
* Neoadjuvant or adjuvant therapy containing an anthracycline that is given within 1-year of randomization into this study counts as first line advanced/metastatic therapy.
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/μL.
Absolute neutrophil count ≥ 1,500/μL.
Platelets ≥ 100,000/μL.
Hemoglobin ≥ 8.0 g/dL
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 <480ms.
Ability to understand and willingness to sign the informed consent form.
No concurrent investigational drug studies are allowed.
Subjects and their partners must be asked to use appropriate contraception. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to remain abstinent (refrain from intercourse) or use at least 1 highly effective contraceptive method (ie, failure rate of <1% per year) in combination with a non-hormonal method for the duration of the study and for 35 days after the last dose of ADI-PEG 20, or for at least 6 months after treatment with GemDoc for FOCBP and 3 months after treatment with GemDoc for male subjects with FOCBP, whichever is the longer duration.
No one method of contraception is 100% effective. Highly effective methods of contraception, when used consistently and correctly, result in low failure rates. These may include hormonal contraceptives (ie, combined hormonal contraceptives associated with inhibition of ovulation: oral, intravaginal, transdermal; progestogen-only hormonal contraceptives associated with inhibition of ovulation: oral, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Highly effective methods of contraception might not always be achievable in the clinical trial setting and, therefore, the most effective alternative can be achieved using methods in combination.
Acceptable birth control methods that result in a failure rate of more than 1% per year include progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide. A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable, but not highly effective, birth control methods.
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 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.
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.
Prior pelvic radiation.
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. 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.
Currently receiving other immunosuppressive agents.
Subjects under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision.
