Clinical Trials List
Protocol NumberPOLARIS2020-001
NCT Number(ClinicalTrials.gov Identfier)NCT04587830
Active
2020-06-01 - 2027-12-31
Phase I/II
Recruiting6
ICD-9V71.1
Observation for suspected malignant neoplasm
Phase 1B Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme
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Trial Applicant
-
Sponsor
Polaris Group
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 蕭庭毅 Division of Radiology
- Pin-Yuan Chen Division of Orthopedics
- Mengting Peng Division of Hematology & Oncology
- 黃盈誠 Division of Orthopedics
- 王俊傑 醫師 Division of Radiation Therapy
- 蔡宏杰 Division of Orthopedics
- 曾振淦 Division of Radiation Therapy
- Peng-Wei Hsu Division of Orthopedics
- 林亞銳 醫師 Division of Orthopedics
- 陳科廷 Division of Orthopedics
- Chi-Ting Liau Division of Hematology & Oncology
- Chi-Cheng Chuang Division of Orthopedics
- 林信吟 醫師 Division of Radiation Therapy
- 盧郁仁 Division of Orthopedics
- 白冰清 Division of Radiation Therapy
- 李丞騏 Division of Orthopedics
- 容世明 Division of Pediatrics
- 高偉恆 醫師 Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林宥潤 Division of Orthopedics
- 袁俊文 Division of Orthopedics
- 李宗翰 Division of Orthopedics
- 李宗翰 醫師 Division of Orthopedics
- 黃郁傑 Division of Radiation Therapy
- 鄭境 Division of Orthopedics
- 石富元 醫師 Division of Orthopedics
- 陳盟翔 Division of Radiology
- 林理涵 Division of Radiology
- 石富元 Division of Orthopedics
- 陳武福 醫師 Division of Orthopedics
- Yu-Li Su Division of Hematology & Oncology
- 何治軍 Division of Orthopedics
- 鄭境効 醫師 Division of Orthopedics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 郭律廷 Division of Orthopedics
- 許峰銘 Division of Radiation Therapy
- YA-FANG CHEN Division of Radiology
- 張克平 Division of Others -
- 吳書丞 醫師 Division of Hematology & Oncology
- - - Division of Orthopedics
- Wei-Wu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- 吳書丞 醫師 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Newly Diagnosed Glioblastoma Multiforme (GBM)
Objectives
Primary Objectives
The primary objective of this study is to assess:
• Safety and tolerability of ADI-PEG 20 in combination with radiotherapy and TMZ in
newly diagnosed GBM
Secondary Objectives
The secondary objectives of this study are to determine:
• The RP2D of ADI-PEG 20 in combination with radiotherapy and TMZ
• PFS at the RP2D
• OS and OS rates at the RP2D
• Pharmacokinetics of ADI-PEG 20 in combination with radiotherapy and TMZ
• Pharmacodynamics of ADI-PEG 20 in combination with radiotherapy and TMZ
• Immunogenicity of ADI-PEG 20 in combination with radiotherapy and TMZ
Test Drug
ADI-PEG 20
Active Ingredient
Arginine deiminase conjugated to polyethylene glycol 20,000 mw
Dosage Form
IVT
Dosage
3.5ml/vial；11.5±1.0mg/ml
Endpoints
Primary Outcome Measures :
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of ADI-PEG 20 in combination with radiotherapy and TMZ [ Time Frame: Through study completion, 2.5 year anticipated ]
Secondary Outcome Measures :
Determine recommended phase 2 dose (RP2D) [ Time Frame: Through study completion, 2.5 year anticipated ]
RP2D will be determined by 3+3 method, depending on the Dose-Limiting Toxicity (DLT).
Measure progression free survival at the RP2D [ Time Frame: Baseline brain MRI is after glioma surgery (if applicable) and prior to subject receiving the first ADI-PEG 20 administration. Scans are to be performed after 1, 3 and 6 months following completion of radiation therapy. ]
Progression free survival was defined as the period of time from randomization to date of tumor progression or death. Tumor measurements must be noted and tumor response status by investigator should be calculated.
Measure overall survival at the RP2D [ Time Frame: Through study completion, 2.5 year anticipated ]
Overall Survival was defined as the period of time from randomization to date of death due to any cause.
Minimum blood plasma concentration [Cmin ] of ADI-PEG 20 [ Time Frame: Blood samples to be collected bi-weekly for 11 weeks, then once every 4 weeks until week36. Sample will be collected prior to ADI-PEG 20 administration ]
A pharmacokinetics measure of minimum ADI-PEG 20 concentration before the next ADI-PED 20 administration
Blood plasma level of arginine and citrulline [ Time Frame: Blood samples to be collected bi-weekly for 11 weeks, then once every 4 weeks until week36. Sample will be collected prior to ADI-PEG 20 administration ]
Pharmacodynamics of ADI-PEG 20 in combination with radiotherapy and TMZ
Plasma levels of antibodies against ADI-PEG 20 [ Time Frame: Through study completion, 2.5 year anticipated ]
Measurement of serum antibodies to ADI-PEG 20 to determine immunogenicity of ADI-PEG 20 in combination with radiotherapy and TMZ
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of ADI-PEG 20 in combination with radiotherapy and TMZ [ Time Frame: Through study completion, 2.5 year anticipated ]
Secondary Outcome Measures :
Determine recommended phase 2 dose (RP2D) [ Time Frame: Through study completion, 2.5 year anticipated ]
RP2D will be determined by 3+3 method, depending on the Dose-Limiting Toxicity (DLT).
Measure progression free survival at the RP2D [ Time Frame: Baseline brain MRI is after glioma surgery (if applicable) and prior to subject receiving the first ADI-PEG 20 administration. Scans are to be performed after 1, 3 and 6 months following completion of radiation therapy. ]
Progression free survival was defined as the period of time from randomization to date of tumor progression or death. Tumor measurements must be noted and tumor response status by investigator should be calculated.
Measure overall survival at the RP2D [ Time Frame: Through study completion, 2.5 year anticipated ]
Overall Survival was defined as the period of time from randomization to date of death due to any cause.
Minimum blood plasma concentration [Cmin ] of ADI-PEG 20 [ Time Frame: Blood samples to be collected bi-weekly for 11 weeks, then once every 4 weeks until week36. Sample will be collected prior to ADI-PEG 20 administration ]
A pharmacokinetics measure of minimum ADI-PEG 20 concentration before the next ADI-PED 20 administration
Blood plasma level of arginine and citrulline [ Time Frame: Blood samples to be collected bi-weekly for 11 weeks, then once every 4 weeks until week36. Sample will be collected prior to ADI-PEG 20 administration ]
Pharmacodynamics of ADI-PEG 20 in combination with radiotherapy and TMZ
Plasma levels of antibodies against ADI-PEG 20 [ Time Frame: Through study completion, 2.5 year anticipated ]
Measurement of serum antibodies to ADI-PEG 20 to determine immunogenicity of ADI-PEG 20 in combination with radiotherapy and TMZ
Inclution Criteria
Inclusion Criteria:
Newly diagnosed, histologically confirmed GBM WHO Grade IV (any wildtype or mutant or gene type, except gliosarcoma), 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. 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.
ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x upper limit normal.
Newly diagnosed, histologically confirmed GBM WHO Grade IV (any wildtype or mutant or gene type, except gliosarcoma), 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. 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.
ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x upper limit normal.
Exclusion Criteria
Exclusion Criteria:
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 .
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.
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 .
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.
The Estimated Number of Participants
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Taiwan
50 participants
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Global
100 participants
