Study on Gene Evolution in Glioma Under Stress Therapy

Genetic Change Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05512325
• Other study ID #: HenanPPH-GRS
• Status: Not yet recruiting
• Start date: December 17, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: August 2022
• Source: Henan Provincial People's Hospital
• Contact: Xingyao Bu, Ph.D
• Phone: 18538297990
• Email: xingyaob[@]zzu.edu.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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;

Related Conditions & MeSH terms

• Genetic Change
• Glioma

Intervention

Drug:
• 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 course of tumor progression, Recording image changes

Locations

Country	Name	City	State
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Henan Provincial People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Different subtypes of glioma have different therapeutic responses to bevacizumab	We evaluated the efficacy of bevacizumab on different subtypes of glioma at recurrence according to delta-VAF and Ratio combined with imaging.The mean change in VAF (delta-VAF) was calculated per patient as the sum of the ontreatmentVAF minus the pretreatment VAF for each detected SNV or indel divided by the number of detected SNVs or indels, we found that the "molecular responce" model could generally be represented in simpler terms through a ratio of ontreatment VAF to pretreatment VAF	96 weeks
Primary	the molecular mechanism of bevacizumab resistance in vivo.	We compared and analyzed the genes before and after bevacizumab treatment according to the gene evolution of ctDNA.To clarify the molecular mechanism of bevacizumab resistance.	144 weeks