Neoadjuvant PD-1 Antibody Alone or Combined With Autologous Glioblastoma Stem-like Cell Antigens-primed DC Vaccines (GSC-DCV) for Patients With Recurrent Glioblastoma：A Phase II, Randomized Controlled, Double Blind Clinical Trial.
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Overall survival (OS)
研究概览
简要总结
Glioblastoma multiforme (GBM) are the most prevalent malignant tumor in central nervous system. At recurrence, no clear standard-of-care therapy is agreed for recurrent GBM (rGBM) and median overall survival is estimated to rarely exceed 6-9 months with effective therapies. Neoadjuvant therapy with anti-PD-1 monoclonal antibodies were confirmed to be helpful to extend survival in rGBM. Vaccine, dendritic cells (DCs) pulsed with glioblastoma stem-like cell (GSC) antigens (GSC-DCV), could extend survival for GBM patients in our previous clinical study (PMID: 30159779). The purpose of this study is to evaluate the safety and efficiency of using the neoadjuvant therapy with PD-1 antibody (Carilizumab) plus DC vaccine (GSC-DCV) in patients with recurrent glioblastoma.
详细描述
This is a phase II randomized controlled clinical study. The purpose of this research is to study the safety and efficacy of Camrelizumab alone or combined with GSC-DCV vaccines in treating patients with recurrent glioblastomas. The participants will be randomly assigned into two group. Patients in group A will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression. Patients in group B will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression. Furthermore, to evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events based on the next generation sequencing.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age from 18 to 70 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or
- •Estimated life expectancy > 3 months.
- •Previous first-line therapy with radiotherapy and chemotherapy, first or second relapse with unequivocal evidence of tumor progression.
- •Pathological diagnosis or molecular diagnosis for lesion this time was confirmed to be recurrent brain glioma (WHO grade 4).
- •Patients with subtotal resection or above of the tumor confirmed with contrast MR within 72 hours after surgery.
- •No high-dose systemic corticosteroids (defined as >10 mg day-1 of prednisone or bio-equivalent for at least seven consecutive days before administration).
- •No antibiotics for at least three consecutive days before administration.
- •Adequate organ function defined by:
- •Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0×10^9/L, platelets ≥100×10^9/L; hemoglobin ≥ 8 g/dL. Hepatic: bilirubin 2×upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5×upper limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine clearance >60 ml/min/1.73 m
- •Electrocardiogram: normal.
- •Written informed consent.
- •Patient should have good follow-up compliance.
排除标准
- •Pregnant or breast-feeding patients.
- •Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with history of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of cortisol.
- •Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
- •Any previous investigational medication within 30 days before first administration of Camrelizumab.
- •History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies.
研究组 & 干预措施
Neoadjuvant PD-1 inhibitor plus DC vaccine
Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, DC vaccines and further PD-1 inhibitor treatment until toxicity or progression.
干预措施: Camrelizumab plus GSC-DCV (Biological)
Neoadjuvant PD-1 inhibitor plus Placebo
Patients will receive neoadjuvant Camrelizumab (PD-1 antibody), followed by surgical resection, placebo and further PD-1 inhibitor treatment until toxicity or progression.
干预措施: Camrelizumab plus Placebo (Biological)
结局指标
主要结局
Overall survival (OS)
时间窗: 24 months
Time from enrollment to the dates of death from any cause or last follow up reported
Progression-free survival (PFS)
时间窗: 12 months
Time from enrollment to the dates of disease progression, death from any cause or last tumor assessment reported between date of first patient enrollment
次要结局
- Number of treatment-related adverse events(12 months)
- Treatment Responses Rate(6 months)