Study on Gene Evolution in Glioma Under Stress Therapy

Официальное название

Study on Gene Evolution and Anti-VEGF Treatment Response of Different Subtypes of Glioma Based on ctDNA

Обзор

Little is known about the evolution of genetic and epigenetic changes that occur in the progression of glioma. We inferred the evolution trajectories of matched pairs of primary tumors and progression tumor in situ fluid (TISF) based on deep whole-genome-sequencing data (ctDNA). A monocentric, Gene grouping controlled trial design was used to select patients. and to compare gene evolution of different subtypes of glioma under therapy. To predict the molecular reaction of bevacizumab treatment, clarify the mechanism of drug resistance of bevacizumab treatment.

Подробное описание

Patient: Adult glioma, pathological diagnosis combined with molecular diagnosis (i.e. IDH- mutant glioma, IDH- mutant glioma with 1p/19q- co-deletion, glioblastoma). The patients were divided into three groups: group A (IDH mutant glioma), group B (IDH mutant with 1p/19q co-deletion oligodendroglioma ) and group C (IDH wild glioblastoma). From the first day after surgery, the ctDNA was extracted with TISF before concurrent chemoradiotherapy as the baseline, and the ctDNA was detected again after concurrent chemoradiotherapy. For the third time, ctDNA was detected in temozolomide intensive chemotherapy. ctDNA was detected for the fourth time when the image showed tumor progression. After the progress, temozolomide combined with bevacizumab was used for chemotherapy. ctDNA was detected 6 weeks after the application of bevacizumab, and ctDNA was re-measured every 6 weeks during the treatment of bevacizumab. At the same time, imaging examination was performed to determine the tumor progress. Check and record adverse events and drug use in detail, and evaluate the compliance of subjects; After TISF tissue extraction, the retained blood samples were sent to simcere Company and Beijing Genetron Health Technology Co. Ltd for ctDNA quantification and detection. To study the differences of gene evolution of different subtypes of glioma under pressure therapy, to clarify the differences of molecular responses of different subtypes of glioma to bevacizumab, and to evaluate the therapeutic effect and safety.

Вмешательства

• Препарат Gene evolution and molecular response under Bevacizumab treatment
  Patients with glioma were routinely treated with temozolomide chemotherapy from the 4th week after operation, for 5 days continuously, once every 4 weeks, with a single dose as follows: Single dose = BSA (body surface area) \* 150mg/m2/day BSA(Body Surface Area)=\[weight (kg)\* height (cm)/3600\]2, According to the molecular pathological grade (WHO CNS5 grade), it is decided whether to combine radiotherapy (GBM combined with radiotherapy) and temozolomide combined with bevacizumab (600mg) in the

Первичные конечные точки

• Different subtypes of glioma have different therapeutic responses to bevacizumab [Срок оценки: 96 weeks]
• the molecular mechanism of bevacizumab resistance in vivo. [Срок оценки: 144 weeks]

Критерии участия

Критерии включения

• Age 18 to 75 years, both male and female (including 18 and 75 years old) glioma;
• Willing to accept treatment and sign informed consent.

Критерии исключения

• Participants with other infection disease or immunodeficiency disease;
• other central infectious diseases;
• malignant tumor of non-nervous system;
• drug abuse;
• severe psychiatric disease;
• uncontrolled diabetes;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

Китай · 1 центр

• Henan Provincial People's Hospital — Чжэнчжоу

Публикации

• Liu G, Bu C, Guo G, Zhang Z, Sheng Z, Deng K, Wu S, Xu S, Bu Y, Gao Y, Wang M, Liu G, Kong L, Li T, Li M, Bu X. Molecular and clonal evolution in vivo reveal a common pathway of distant relapse gliomas. iScience. 2023 Aug 2;26(9):107528. doi: 10.1016/j.isci.2023.107528. eCollection 2023 Sep 15. PMID 37649695
• Liu G, Bu C, Guo G, Zhang Z, Sheng Z, Deng K, Wu S, Xu S, Bu Y, Gao Y, Wang M, Liu G, Kong L, Li T, Li M, Bu X. Genomic alterations of oligodendrogliomas at distant recurrence. Cancer Med. 2023 Aug;12(16):17171-17183. doi: 10.1002/cam4.6327. Epub 2023 Aug 2. PMID 37533228

Идентификаторы

NCT: NCT05512325 · HenanPPH-GRS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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