ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects with Glioblastoma Multiforme

Launched by POLARIS GROUP · Oct 8, 2020

Keywords

ClinConnect Summary

This clinical trial, called ADI-PEG 20 Plus Radiotherapy and Temozolomide, is studying a new treatment approach for patients with Glioblastoma Multiforme (GBM), a type of aggressive brain cancer. The study is looking to see if adding a medication called ADI-PEG 20 to standard treatments, which include radiation therapy and a chemotherapy drug called temozolomide (TMZ), can improve outcomes for patients. The trial is currently recruiting participants aged 20 to 75 who have been newly diagnosed with GBM.

To be eligible for the trial, participants must have a confirmed diagnosis of GBM, be able to perform daily activities with some assistance (a Karnofsky Performance Status of at least 60), and should not have received any prior cancer treatments. Participants will receive either the ADI-PEG 20 medication or a placebo (a dummy treatment that has no active ingredients) alongside the standard therapy. Throughout the study, participants can expect regular check-ins with the research team to monitor their health and response to the treatment. It's important to note that both male and female participants who are capable of becoming pregnant must agree to use effective contraception during the study to prevent pregnancy.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Newly diagnosed, histologically confirmed glioblastoma, IDH-wildtype and the WHO Grade 4 of astrocytoma, IDH-mutant by WHO 2021 classification of brain tumors, non-resectable or partially resected or resected.
• • 2. Age 20 - 75 years.
• • 3. Karnofsky Performance Status (KPS) ≥ 60.
• • 4. Expected life expectancy ≥16 weeks.
• • 5. Stable or decreasing corticosteroids (5 mg/day dexamethasone or equivalent) within 5 days before the first dose of ADI-PEG 20.
• • 6. No prior systemic therapy, immunotherapy, investigational agent, or radiation therapy.
• • 7. Recovered from any prior surgery and no major surgery within 2 weeks of initiating treatment (other than GBM surgery). Surgery for placement of vascular access devices is acceptable.
• • 8. Female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study and for at least 30 days after the last administration of ADI-PEG 20 or placebo and at least 6 months after the last administration of TMZ. Male partners of female subjects and female partners of male subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study if they are of childbearing potential. Females of childbearing potential must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this subject is deemed eligible. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual period for at least 12 months).
• • 9. Informed consent must be obtained prior to study initiation.
• • 10. No concurrent investigational studies are allowed.
• • 11. Absolute neutrophil count (ANC) ≥ 1500/μL.
• • 12. Platelets ≥ 100,000/μL.
• • 13. Serum uric acid ≤ 8 mg/dL (with or without medication control).
• • 14. Creatinine clearance must be ≥ 40 mL/min/1.73 m2 (calculated using the Cockcroft-Gault equation: calculated creatinine clearance = (140-age (yrs)) × body weight (kg) (×0.85 if female) / 72 × serum creatinine (mg/dl).
• • 15. Total bilirubin ≤ 2 x upper limit of normal.
• • 16. ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x upper limit normal.
• Exclusion Criteria:
• • 1. Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
• • 2. Pregnancy or lactation.
• • 3. Expected non-compliance.
• • 4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
• • 5. 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 or in the opinion of the investigator will not affect patient outcome.
• • 6. Subjects who had been treated with ADI-PEG 20 previously.
• • 7. History of uncontrolled seizure disorder not related to underlying cancer.
• • 8. Known HIV positivity, or active hepatitis B infection, or active hepatitis C infection (testing not required).
• • 9. Allergy to pegylated compounds.
• • 10. Allergy to E. coli drug products (such as GMCSF).
• • 11. Allergy to TMZ or any of its components.
• • 12. History of hypersensitivity to dacarbazine.
• • 13. Placement of Gliadel wafer at surgery.
• • 14. Having a co-existing condition requiring systemic treatment with either corticosteroids or immunosuppressive medication.