Study on Gene Evolution in Glioma Under Stress Therapy

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Genetic Change
• Intervention / Treatment: Drug: Gene evolution and molecular response under Bevacizumab treatment

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Xingyao Bu, Ph.D; Phone Number: 18538297990; Email: xingyaob@zzu.edu.cn
• Study Contact Backup: Name: Huibin Ning, Ph.D; Phone Number: 15981849054; Email: situhailuo@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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;

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gene evolution of glioma in vivo; Group A: gene evolution with relapsed. From the first day after the operation, the ctDNA was extracted from TISF before concurrent chemoradiotherapy as the baseline, and then the ctDNA was detected again after concurrent chemoradiotherapy. For the third time, ctDNA was detected in intensive chemotherapy with temozolomide. The image showed that the tumor progress was detected for the fourth time, and the ctDNA was detected for the fifth time when the tumor recurred. 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,
Gene evolution and molecular response under Bevacizumab treatment; After the recurrence, temozolomide combined with bevacizumab was used for chemotherapy, After bevacizumab was applied after six week , ctDNA is tested every six weeks. temozolomide combined with bevacizumab (600mg) in the course of tumor progression once a month.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Henan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 17, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: August 21, 2022
• First Submitted That Met QC Criteria: August 21, 2022
• First Posted (Actual): August 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 25, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: gene evolution, ctDNA, molecular response, Bevacizumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: HenanPPH-GRS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No