Combining ADI-PEG 20 with radiotherapy and Temozolomide for glioblastoma

Phase 1-2 Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects with Newly Diagnosed Glioblastoma Multiforme (GBM)

This study is testing if adding a new treatment called ADI-PEG 20 to standard radiotherapy and Temozolomide can help people with newly diagnosed glioblastoma live longer and feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 20 Years to 75 Years
• Sex: All
• Sponsor: Polaris Group (industry)
• Drugs / interventions: immunotherapy, radiation
• Locations: 10 sites (Hwasun-gun, Jeollanam-do and 9 other locations)
• Trial ID: NCT04587830 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 study that investigates the efficacy of ADI-PEG 20 in combination with the Stupp Protocol radiotherapy and Temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme. Participants will receive either ADI-PEG 20 or a placebo weekly, alongside standard treatment, and may continue treatment for up to two years if there is no disease progression. MRI assessments will be conducted at various intervals to monitor treatment response and disease status.

Who should consider this trial

Good fit: Ideal candidates are adults aged 20 to 75 with newly diagnosed, histologically confirmed glioblastoma who have not received prior systemic therapy or radiation.

Not a fit: Patients with prior systemic therapy, immunotherapy, or significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve survival outcomes and quality of life for patients with glioblastoma multiforme.

How similar studies have performed: While this study employs a novel combination approach, similar studies have shown promise in enhancing treatment efficacy for glioblastoma.

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.

Where this trial is running

Hwasun-gun, Jeollanam-do and 9 other locations

• Chonnam National University Hwasun Hospital — Hwasun-gun, Jeollanam-do, Korea, Republic of (RECRUITING)
• Seoul National University Hospital — Seoul, Jongno-gu, Korea, Republic of (RECRUITING)
• Seoul St. Mary's Hospital, The Catholic University of Korea — Seoul, Seocho-gu, Korea, Republic of (RECRUITING)
• Severance Hospital Yonsei University — Seoul, Seodaemun-gu, Korea, Republic of (RECRUITING)
• Seoul National University Bundang Hospital — Gyeonggi-do, Seongnam, Korea, Republic of (RECRUITING)
• Chang Gung-Medical Foundation-Keelung (CGMF-KL) — Keelung, Anle Dist, Taiwan (RECRUITING)
• Chang Gung Memorial Hospital, Linkou Branch — Taoyuan, Guishan Dist, Taiwan (RECRUITING)
• Chang Gung Medical Foundation-Kaohsiung — Kaohsiung, Niaosong Dist, Taiwan (RECRUITING)
• Mackay Memorial Hospital-Tamsui Branch — New Taipei City, Tamsui Dist, Taiwan (RECRUITING)
• National Taiwan University Hospital — Taipei City, Zhongzheng Dist, Taiwan (RECRUITING)

Study contacts

• Principal investigator: Kuo-Chen Wei, M.D. — Chang Gung Memorial Hospital
• Study coordinator: John Bomalaski, M.D.

Conditions: Glioblastoma Multiforme, argininosuccinate synthetase, arginine, arginine deiminase