Study on Gene Evolution in Glioma Under Stress Therapy

NCT05512325 | Not Yet Recruiting

• 1 other identifier: HenanPPH-GRS
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Genetic Change

Keywords

gene evolution, ctDNA, molecular response, Bevacizumab

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

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

Interventions

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

Gene evolution and molecular response under Bevacizumab treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Henan Provincial People's Hospital: lead

Study Sites (1)

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

A small amount of TISF was harvested from the implanted reservoir(Intra-operative retention) during postoperative progression of 20 glioma patients under stress therapy. At the same time, blood samples (5ml) for germline DNA control were also acquired. Fresh tumor tissues were obtained for comparing evolution analysis with TISF ctDNA under bevacizumab treatment.

Central Study Contacts

Xingyao Bu, Ph.D

CONTACT

18538297990; xingyaob@zzu.edu.cn

Huibin Ning, Ph.D

CONTACT

15981849054; situhailuo@163.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2022
• First Posted: August 23, 2022
• Study Start: December 17, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 27, 2022

Record last verified: 2022-08

Locations

CN (1)