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NCT Number: NCT05512325

Study on Gene Evolution in Glioma Under Stress Therapy

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.

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Key information

Conditions

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

Location contact

Xingyao Bu

CONTACT

[email protected]

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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;

Treatment and study plan

Gene evolution and molecular response under Bevacizumab treatment

Drug

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

Primary outcomes

  1. Different subtypes of glioma have different therapeutic responses to bevacizumab

    Time frame: 96 weeks

    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

  2. the molecular mechanism of bevacizumab resistance in vivo.

    Time frame: 144 weeks

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Huibin Ning, Ph.D

CONTACT

[email protected]

15981849054

Xingyao Bu, Ph.D

CONTACT

[email protected]

18538297990

Sponsors and collaborators

Lead sponsor

Henan Provincial People's Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Aug 23, 2022
Registry last updated
Sep 27, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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