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

NCT04587830 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: POLARIS2020-001
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 10

Brief Summary

A randomized, double-blind, placebo-controlled study. Weekly ADI-PEG 20 (36 mg/m2) or placebo will be combined with Stupp Protocol (Stupp 2005) radiotherapy and TMZ

Conditions

Glioblastoma Multiforme (GBM)

Keywords

argininosuccinate synthetase; arginine; arginine deiminase

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  In the ADI-PEG 20 treated arm compared to the placebo arm, and determine if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment

  Through study completion, 2.5 year anticipated

Secondary Outcomes (7)

• Progression-free survival (PFS)

  Through study completion, 2.5 year anticipated

• Duration of response (DOR)

  Through study completion, 2.5 year anticipated

• Tumor response rate

  Through study completion, 2.5 year anticipated

• Safety and tolerability of ADI-PEG 20

  Through study completion, 2.5 year anticipated

• Pharmacokinetics of ADI-PEG 20

  Up to week 52 or End of treatment visit

Study Arms (2)

ADI-PEG 20 plus Radiotherapy and Temozolomide

EXPERIMENTAL

ADI-PEG 20 Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 4 weeks of surgery (diagnostic and/or resection) Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous

Drug: ADI-PEG 20; Drug: Temozolomide

Placebo plus Radiotherapy and Temozolomide

PLACEBO COMPARATOR

Placebo Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 4 weeks of surgery (diagnostic and/or resection) Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous

Drug: Temozolomide; Drug: Placebo

Interventions

ADI-PEG 20 DRUG

Investigational Medicine

ADI-PEG 20 plus Radiotherapy and Temozolomide

Temozolomide DRUG

Radiotherapy and TMZ are standard front-line therapy for newly diagnosed GBM.

ADI-PEG 20 plus Radiotherapy and Temozolomide; Placebo plus Radiotherapy and Temozolomide

Placebo DRUG

Investigational Medicine

Placebo plus Radiotherapy and Temozolomide

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 20 - 75 years.
• Karnofsky Performance Status (KPS) ≥ 60.
• Expected life expectancy ≥16 weeks.
• Stable or decreasing corticosteroids (5 mg/day dexamethasone or equivalent) within 5 days before the first dose of ADI-PEG 20.
• No prior systemic therapy, immunotherapy, investigational agent, or radiation therapy.
• 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.
• 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).
• Informed consent must be obtained prior to study initiation.
• No concurrent investigational studies are allowed.
• Absolute neutrophil count (ANC) ≥ 1500/μL.
• Platelets ≥ 100,000/μL.
• Serum uric acid ≤ 8 mg/dL (with or without medication control).
• 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).
• Total bilirubin ≤ 2 x upper limit of normal.

You may not qualify if:

• 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.
• Pregnancy or lactation.
• Expected non-compliance.
• 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.
• 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.
• Subjects who had been treated with ADI-PEG 20 previously.
• History of uncontrolled seizure disorder not related to underlying cancer.
• Known HIV positivity, or active hepatitis B infection, or active hepatitis C infection (testing not required).
• Allergy to pegylated compounds.
• Allergy to E. coli drug products (such as GMCSF).
• Allergy to TMZ or any of its components.
• History of hypersensitivity to dacarbazine.
• Placement of Gliadel wafer at surgery.
• Having a co-existing condition requiring systemic treatment with either corticosteroids or immunosuppressive medication.

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (10)

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, 58128, South Korea

Location

Seoul National University Hospital

Seoul, Jongno-gu, 03080, South Korea

Location

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, Seocho-gu, 06591, South Korea

Location

Severance Hospital Yonsei University

Seoul, Seodaemun-gu, 03722, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, Seongnam, 13620, South Korea

Location

Chang Gung-Medical Foundation-Keelung (CGMF-KL)

Keelung, Anle Dist, 204201, Taiwan

Location

Chang Gung Memorial Hospital, Linkou Branch

Taoyuan District, Guishan Dist, 333423, Taiwan

Location

Chang Gung Medical Foundation-Kaohsiung

Kaohsiung City, Niaosong Dist, 833401, Taiwan

Location

Mackay Memorial Hospital-Tamsui Branch

New Taipei City, Tamsui Dist, 251404, Taiwan

Location

National Taiwan University Hospital

Taipei, Zhongzheng Dist, 100229, Taiwan

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

ADI PEG20; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kuo-Chen Wei, M.D.

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: October 14, 2020
• Study Start: September 14, 2020
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): May 30, 2027
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5); TW (5)