Clinical trial NCT04587830: ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects with Glioblastoma Multiforme
Official title: Phase 1-2 Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects with Newly Diagnosed Glioblastoma Multiforme (GBM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glioblastoma Multiforme (GBM)
Keywords: argininosuccinate synthetase
arginine
arginine deiminase
Lead sponsor: Polaris Group
Sponsor class: INDUSTRY
First posted: 2020-10-14
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Through study completion, 2.5 year anticipated
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Through study completion, 2.5 year anticipated
measure: Duration of response (DOR)
timeFrame: Through study completion, 2.5 year anticipated
measure: Tumor response rate
timeFrame: Through study completion, 2.5 year anticipated
measure: Safety and tolerability of ADI-PEG 20
timeFrame: Through study completion, 2.5 year anticipated
measure: Pharmacokinetics of ADI-PEG 20
timeFrame: Up to week 52 or End of treatment visit
measure: Pharmacodynamics of ADI-PEG 20
timeFrame: Up to week 52 or End of treatment visit
measure: Immunogenicity of ADI-PEG 20
timeFrame: Up to week 52 or End of treatment visit
Other outcomes:
Locations:
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital, The Catholic University of Korea
state: Seocho-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University
state: Seodaemun-gu
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Seongnam
city: Keelung
country: Taiwan
facility: Chang Gung-Medical Foundation-Keelung (CGMF-KL)
state: Anle Dist
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou Branch
state: Guishan Dist
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation-Kaohsiung
state: Niaosong Dist
city: New Taipei City
country: Taiwan
facility: Mackay Memorial Hospital-Tamsui Branch
state: Tamsui Dist
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
state: Zhongzheng Dist
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Kuo-Chen Wei, M.D.
role: PRINCIPAL_INVESTIGATOR
References: