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

NCT ID: NCT04587830

Last Updated: 2025-08-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-14
• Study Completion Date: 2027-05-30

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

Detailed Description

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 as noted for the Phase 1 portion. Furthermore, ADI-PEG 20 or placebo treatment may continue after adjuvant TMZ if there is no progressive disease, for up to a total of 2 years of ADI-PEG 20 or placebo treatment. In addition, after 24 weeks (6 cycles) subjects may also continue adjuvant TMZ along with ADI-PEG 20 or placebo, in the absence of disease progression, as noted above, if clinically indicated in the investigator's judgement. MRI is to be performed post-surgery(biopsy), and then at 1, 3 and 6 months after completion of radiotherapy and then every 3 months for up to 24 months.

Conditions

Glioblastoma Multiforme (GBM)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ADI-PEG 20 plus Radiotherapy and Temozolomide

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

Group Type: EXPERIMENTAL

ADI-PEG 20

Intervention Type: DRUG

Investigational Medicine

Temozolomide

Intervention Type: DRUG

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

Placebo plus Radiotherapy and Temozolomide

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

Group Type: PLACEBO_COMPARATOR

Temozolomide

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Investigational Medicine

Interventions

ADI-PEG 20

Investigational Medicine

Intervention Type: DRUG

Temozolomide

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

Intervention Type: DRUG

Placebo

Investigational Medicine

Intervention Type: DRUG

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Polaris Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kuo-Chen Wei, M.D.

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, South Korea

Seoul National University Hospital

Seoul, Jongno-gu, South Korea

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

Seoul, Seocho-gu, South Korea

Severance Hospital Yonsei University

Seoul, Seodaemun-gu, South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, Seongnam, South Korea

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

Keelung, Anle Dist, Taiwan

Chang Gung Memorial Hospital, Linkou Branch

Taoyuan District, Guishan Dist, Taiwan

Chang Gung Medical Foundation-Kaohsiung

Kaohsiung City, Niaosong Dist, Taiwan

Mackay Memorial Hospital-Tamsui Branch

New Taipei City, Tamsui Dist, Taiwan

National Taiwan University Hospital

Taipei, Zhongzheng Dist, Taiwan

Countries

South Korea; Taiwan

Other Identifiers

POLARIS2020-001

Identifier Type: -

Identifier Source: org_study_id