Genetic ChangeNCT05512325
Study on Gene Evolution in Glioma Under Stress Therapy
An observational study of Genetic Change, run by Henan Provincial People's Hospital at 1 site in China.
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Genetic Change
- What is being tested?
- Gene evolution and molecular response under Bevacizumab treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 17 Dec 2022to 31 Dec 2026
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Age 18 to 75 years, both male and female (including 18 and 75 years old) glioma;
- Willing to accept treatment and sign informed consent.
Who cannot join
- 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;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Henan Provincial People's Hospital
Zhengzhou, Henan, 450003
Xingyao Bu, xingyaob@zzu.edu.cn
About this study
Official title: 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.
Read the 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.
- Conditions
- Genetic Change
- Being tested
- Gene evolution and molecular response under Bevacizumab treatment
- Keywords
- gene evolution, ctDNA, molecular response, Bevacizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gene evolution and molecular response under Bevacizumab treatmentDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Gene evolution and molecular response under Bevacizumab treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 144 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2022
- Study start17 Dec 2022 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Genetic ChangeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Henan Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05512325
- Sponsor's protocol ID
- HenanPPH-GRS
- Status last verified
- Aug 2022
- First submitted
- 21 Aug 2022
- Last updated
- 27 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37649695Liu 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.
PubMed 37533228
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on Gene Evolution and Anti-VEGF Treatment Response of Different Subtypes of Glioma Based on ctDNA
- ClinicalTrials.gov ID
- NCT05512325
- Acronym / sponsor ID
- HenanPPH-GRS
- Conditions
- Genetic Change
- Keywords
- gene evolution, ctDNA, molecular response, Bevacizumab
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Henan Provincial People's HospitalUniversity, hospital or other
- Study start
- 17 Dec 2022 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Drug: Gene evolution and molecular response under Bevacizumab treatmentAfter 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Age 18 to 75 years, both male and female (including 18 and 75 years old) glioma;
- Willing to accept treatment and sign informed consent.
Key exclusion criteria (6 listed)
- Participants with other infection disease or immunodeficiency disease;
- other central infectious diseases;
- malignant tumor of non-nervous system;
- drug abuse;
- severe psychiatric disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gene evolution and molecular response under Bevacizumab treatmentPatients 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 | Drug | Gene evolution and molecular response under Bevacizumab treatment |
Primary outcome
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
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Derived from this study: PubMed 37649695Liu 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.
- Derived from this study: PubMed 37533228Liu 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Genetic Change, run by Henan Provincial People's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xingyao Bu, Ph.D (18538297990, xingyaob@zzu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Different subtypes of glioma have different therapeutic responses to bevacizumab (time frame: 96 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05512325, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.