Phase 1-2 Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme (GBM)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 10
- 主要终点
- Overall survival (OS)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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) ≥
- •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
- •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.
- •ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x upper limit normal.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: ADI-PEG 20 (Drug)
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
干预措施: Temozolomide (Drug)
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
干预措施: Temozolomide (Drug)
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
干预措施: Placebo (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: Through study completion, 2.5 year anticipated
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
次要结局
- 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)
- Pharmacodynamics of ADI-PEG 20(Up to week 52 or End of treatment visit)
- Immunogenicity of ADI-PEG 20(Up to week 52 or End of treatment visit)