Comprehensive Analysis of Chemotherapy and Targeted Therapy Outcomes in Recurrent Malignant Gliomas: Large Single-Center Observational Cohort Study (GLIOTARG)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
GLIOTARG trial is a large single-center observational cohort study designed to investigate chemotherapy and targeted therapy outcomes in recurrent malignant gliomas. The study includes patients with molecularly confirmed diagnoses according to the World Health Organization (WHO) 2021 classification of Central Nervous System (CNS) tumors: glioblastomas (IDH-wildtype, WHO grade 4), astrocytomas (IDH-mutant, WHO grade 3-4), and pleomorphic xanthoastrocytomas (WHO grade 2-3).
详细描述
Malignant gliomas represent the most common and aggressive category of primary malignant brain tumors in adults. Despite multimodal treatment approaches, the prognosis for patients with high-grade gliomas remains poor, with the vast majority ultimately developing disease progression or recurrence. When recurrence occurs, therapeutic options become limited and their efficacy modest. In recurrent glioblastoma, progression-free survival (PFS) and overall survival (OS) are measured in months, while in anaplastic astrocytomas (WHO grade 3-4), these outcomes similarly do not extend beyond one year after second-line therapy
While numerous clinical trials have investigated specific agents in selected populations, real-world data (RWD) on the sequential treatment of recurrent gliomas across multiple lines of therapy remain scarce. By design, these studies often enroll highly selected patients and may not fully represent the heterogeneous, heavily pretreated population encountered in routine clinical practice. Consequently, the comparative effectiveness of different chemotherapy regimens - including bevacizumab-containing schedules (e.g., with irinotecan), nitrosoureas, and platinum compounds - as they are used sequentially in the second, third, and subsequent lines is not well established. For the rare subset of patients harboring a BRAF mutation, targeted therapy with BRAF ± MEK inhibitors may represent an additional option, though real-world evidence in the recurrent setting remains limited. There is a particular lack of large-scale, real-world evidence on the cumulative impact of these sequential therapies on long-term outcomes such as overall survival and progression-free survival across multiple treatment episodes.
The GLIOTARG trial is designed to address this evidence gap. This large, single-center, retrospective and prospective observational cohort study aims to provide a comprehensive analysis of treatment patterns and clinical outcomes in a cohort of approximately 1000 patients with recurrent malignant gliomas treated at the N.N. Blokhin National Medical Research Center of Oncology between 2005 and 2025. By including only patients with molecularly confirmed diagnoses according to the WHO 2021 classification (including IDH-wildtype glioblastomas, IDH-mutant astrocytomas grade 3-4, and pleomorphic xanthoastrocytomas grade 2-3), this study ensures diagnostic precision and alignment with modern neuro-oncological standards.
The primary objective is to evaluate overall survival in a real-world clinical practice setting. Secondary objectives include assessing progression-free survival according to treatment modality, starting with the initial chemoradiotherapy (PFS1), followed by first-line (PFS2), second-line (PFS3), and subsequent lines of drug therapy. The study will specifically compare the efficacy of bevacizumab-containing regimens versus non-bevacizumab chemotherapies, investigate the role of BRAF ± MEK inhibitors in BRAF-mutant tumors, and analyze outcomes in rare histological subtypes such as pleomorphic xanthoastrocytomas. The ultimate goal is to provide a practical, evidence-based algorithm to guide the optimal sequencing of drug therapy in recurrent malignant gliomas, integrating clinical and molecular factors.
The study will pool comprehensive clinical, pathological, and treatment-related data from patients diagnosed with recurrent malignant gliomas over a 20-year period (2005-2025). Data to be collected for each patient will include:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of initial brain tumor diagnosis;
- •Histologically confirmed diagnosis of malignant glioma, including:
- •Glioblastoma, IDH-wildtype (WHO grade 4)
- •Astrocytoma, IDH-mutant (WHO grade 3-4)
- •Pleomorphic xanthoastrocytoma (WHO grade 2-3)
- •Molecularly confirmed diagnosis according to WHO 2021 classification (with available data on IDH1/2, BRAF, 1p/19q, and MGMT status where applicable);
- •Documented disease recurrence or progression with available treatment-related data in medical records to assess at least one of the study outcome measures
排除标准
- •Age < 18 years at initial diagnosis;
- •Absence of molecular-genetic confirmation of the tumor (according to WHO 2021 classification);
- •Lack of documented disease recurrence or progression, or insufficient treatment-related data in medical records to assess at least one of the study outcome measures;
- •Prior participation in clinical trials with unblinded investigational agents where data cannot be extracted (except where data are available and verifiable);
- •Synchronous primary malignant neoplasms.
研究组 & 干预措施
Glioblastoma, IDH-wildtype
Patients with histologically and molecularly confirmed diagnosis of glioblastoma according to the WHO 2021 classification. Tumors are characterized by absence of IDH1/2 mutations (IDH-wildtype), WHO grade 4, and typically exhibit one or more of the following molecular features: TERT promoter mutation, EGFR gene amplification, +7/-10 chromosome copy-number changes. This cohort includes only de novo (primary) glioblastomas. Astrocytomas that have secondarily progressed to glioblastoma (IDH-mutant) were excluded
干预措施: Bevacizumab-Containing Regimens (Drug)
Glioblastoma, IDH-wildtype
Patients with histologically and molecularly confirmed diagnosis of glioblastoma according to the WHO 2021 classification. Tumors are characterized by absence of IDH1/2 mutations (IDH-wildtype), WHO grade 4, and typically exhibit one or more of the following molecular features: TERT promoter mutation, EGFR gene amplification, +7/-10 chromosome copy-number changes. This cohort includes only de novo (primary) glioblastomas. Astrocytomas that have secondarily progressed to glioblastoma (IDH-mutant) were excluded
干预措施: Non-Bevacizumab Regimens (Drug)
Glioblastoma, IDH-wildtype
Patients with histologically and molecularly confirmed diagnosis of glioblastoma according to the WHO 2021 classification. Tumors are characterized by absence of IDH1/2 mutations (IDH-wildtype), WHO grade 4, and typically exhibit one or more of the following molecular features: TERT promoter mutation, EGFR gene amplification, +7/-10 chromosome copy-number changes. This cohort includes only de novo (primary) glioblastomas. Astrocytomas that have secondarily progressed to glioblastoma (IDH-mutant) were excluded
干预措施: BRAF ± MEK Targeted Therapy (Drug)
Astrocytoma, IDH-mutant
Patients with histologically and molecularly confirmed diagnosis of astrocytoma according to the WHO 2021 classification. Tumors are characterized by presence of IDH1 or IDH2 mutations (IDH-mutant), WHO grade 3 or 4, and absence of 1p/19q codeletion. Grade 4 astrocytomas (formerly known as "IDH-mutant glioblastoma") additionally exhibit microvascular proliferation and/or necrosis.
干预措施: Bevacizumab-Containing Regimens (Drug)
Astrocytoma, IDH-mutant
Patients with histologically and molecularly confirmed diagnosis of astrocytoma according to the WHO 2021 classification. Tumors are characterized by presence of IDH1 or IDH2 mutations (IDH-mutant), WHO grade 3 or 4, and absence of 1p/19q codeletion. Grade 4 astrocytomas (formerly known as "IDH-mutant glioblastoma") additionally exhibit microvascular proliferation and/or necrosis.
干预措施: Non-Bevacizumab Regimens (Drug)
Pleomorphic Xanthoastrocytoma
Patients with histologically and molecularly confirmed diagnosis of pleomorphic xanthoastrocytoma according to the WHO 2021 classification. Tumors are characterized by pleomorphic, lipidized astrocytes, often with BRAF V600E mutations (present in approximately 60-70% of cases). Both WHO grade 2 and grade 3 (anaplastic) variants were included. Anaplastic features include increased mitotic activity (≥ 5 mitoses per 10 high-power fields) and may show necrosis. All pleomorphic xanthoastrocytomas, regardless of BRAF mutation status, were included.
干预措施: Bevacizumab-Containing Regimens (Drug)
Pleomorphic Xanthoastrocytoma
Patients with histologically and molecularly confirmed diagnosis of pleomorphic xanthoastrocytoma according to the WHO 2021 classification. Tumors are characterized by pleomorphic, lipidized astrocytes, often with BRAF V600E mutations (present in approximately 60-70% of cases). Both WHO grade 2 and grade 3 (anaplastic) variants were included. Anaplastic features include increased mitotic activity (≥ 5 mitoses per 10 high-power fields) and may show necrosis. All pleomorphic xanthoastrocytomas, regardless of BRAF mutation status, were included.
干预措施: Non-Bevacizumab Regimens (Drug)
Pleomorphic Xanthoastrocytoma
Patients with histologically and molecularly confirmed diagnosis of pleomorphic xanthoastrocytoma according to the WHO 2021 classification. Tumors are characterized by pleomorphic, lipidized astrocytes, often with BRAF V600E mutations (present in approximately 60-70% of cases). Both WHO grade 2 and grade 3 (anaplastic) variants were included. Anaplastic features include increased mitotic activity (≥ 5 mitoses per 10 high-power fields) and may show necrosis. All pleomorphic xanthoastrocytomas, regardless of BRAF mutation status, were included.
干预措施: BRAF ± MEK Targeted Therapy (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From date of initial brain tumor diagnosis until date of death or last contact with the patient, assessed up to 5 years (censored)
Time from the date of initial brain tumor diagnosis to the date of death from any cause or last contact with the patient (censored)
次要结局
- Progression-Free Survival 1 (PFS1)(From start of chemoradiotherapy until date of first progression or censoring at the start of first-line treatment, assessed up to 5 years)
- Progression-Free Survival 2 (PFS2)(From start of first-line therapy until date of progression or censoring at last instrumental follow-up, assessed up to 5 years)
- Progression-Free Survival 3 (PFS3)(From start of second-line therapy until date of progression or censoring at last instrumental follow-up, assessed up to 5 years)
- Progression-Free Survival 4 (PFS4)(From start of third-line therapy until date of progression or censoring at last instrumental follow-up, assessed up to 5 years)
- Progression-Free Survival 5 (PFS5)(From start of fourth-line therapy until date of progression or censoring at last instrumental follow-up, assessed up to 20 years)
研究者
David Khalafyan
Study Chair
Blokhin's Russian Cancer Research Center