Glioblastoma, IDH-wildtypeTHERABIOME-GBMNCT05326334
THERApeutic Outcomes Related to Gut microBIOME in Glioblastoma (GBM) Patients Receiving Chemo-radiation (THERABIOME-GBM)
An observational study of Glioblastoma, IDH-wildtype, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
This is a pilot or feasibility study to test the study plan and to find out whether enough participants will join a larger study and accept the study procedures. Eligible participants (adults with newly diagnosed glioblastoma multiforme [GBM] and had a good tumour resection [>= 70% of initial tumour volume] and plan… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, IDH-wildtype
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 2 Mar 2023to Sep 2029
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: IDH-1 R132H wild type WHO grade 4 glioblastoma multiforme is the most common type of primary brain cancer. This study enrolled prognostically similar patients (at least 70% tumour volume resection, ECOG PS 0-2, eligible to receive RT 60 Gy/30 fractions)
Who may be able to join
- Patients with newly diagnosed WHO grade 4 glioblastoma, IDH-1 R132H wild type
- Maximum safe resection (≥70% of initial tumor volume resected)
- Age ≥ 18
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 or ECOG 2 if on ≤ 8 mg/day of dexamethasone (or bioequivalent)
- Plan to receive 60 Gy / 30 fractions of radiation with temozolomide within 12 weeks of surgery
- Patient or substitute decision maker able to provide written informed consent
Who cannot join
- Metastatic cancer or secondary cancer that could affect interpretation of primary and secondary study outcomes
- Receiving additional systemic therapy / clinical intervention for glioblastoma that would prevent a uniform treatment cohort with temozolomide and radiation x 6 weeks followed by adjuvant temozolomide 150-200 mg/m2 on days 1-5 every 28 days for up to 6 cycles.*
- Inability to collect study stool samples
- Any diagnosis or medical condition, physical and / or psychological, that the investigator feels precludes the patient from participation in the study.
- If there is a new standard of care treatment for newly diagnosed GBM before the first patient is enrolled (e.g., Optune Tumor Treating Fields), then we will allow all patients on this study to adopt the new standard of care therapy. To allow for maximum patient accrual, if patient chooses to enroll on an open label randomized therapeutic study whereby the control arm involves only the standard of care treatment, then patients enrolled in the control arm could be eligible for this study at the discretion of the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6
Terry L. Ng, MD, 613-737-7700
About this study
Official title: THERApeutic Outcomes Related to Gut microBIOME in Glioblastoma (GBM) Patients Receiving Chemo-radiation: A Prospective Observational Study
This is a pilot or feasibility study to test the study plan and to find out whether enough participants will join a larger study and accept the study procedures. Eligible participants (adults with newly diagnosed glioblastoma multiforme [GBM] and had a good tumour resection [>= 70% of initial tumour volume] and plan to receive 6 weeks of chemoradiation followed by up to 6 months of chemotherapy) are asked to donate their own stool samples at 4 different time points during their treatment course. Participants will also complete a 7-day diet diary and two questionnaires about their health-related quality of life.
Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer in adults. The current best evidence-proven treatment for GBM includes maximum safe tumour resection, brain radiation over a 6-week period given with chemotherapy pills called temozolomide (Brand name: Temodal or Temodar), followed by approximately 6 months / cycles of temozolomide. Despite these treatments, the average life expectancy is generally less than 2 years.
Read more
Researchers are recognizing that the immune system has an important role in directing the effectiveness of chemotherapy, radiation, and newer therapies such as immunotherapies. Some immunotherapies have been quite successful in improving cancer control and survival in other cancers like melanoma (an aggressive skin cancer), but when these drugs were given to patients with GBM, there appeared to only be a small effect. Therefore, finding ways to make existing and new treatments work better should be a priority. Recent scientific studies have shown that the bacteria that make up our stool, often referred to as the gut microbiome, play a major role in regulating the immune system. For example, researchers were able to make patients with melanoma who previously did not respond to immunotherapy become responsive to the treatment after receiving a stool transplant from responders to immunotherapy. This provides proof of concept that we could modify the body's immune environment to favour cancer killing by changing a person's gut bacteria environment.
The role of the gut bacteria in patients with brain cancer is poorly understood as very few studies have been published about it in this population. We believe that understanding the composition of the gut microbiome and how it relates to the effectiveness and side effects of treatments in GBM patients will be an important first step to understanding how we can modify the gut microbiome to improve outcomes for patients living with GBM.
Read the detailed description
This is a prospective observational study designed to assess changes in the gut microbial composition and diversity in prospectively collected stool samples at important time points throughout GBM treatment and surveillance and to correlate that with patient survival outcomes and radiation necrosis.
Objectives:
- To assess feasibility of stool sample collection, banking, and analysis throughout the treatment course of GBM patients.
- To determine the association of gut microbiome composition with survival outcomes in isocitrate dehydrogenase (IDH) type 1 wild type glioblastoma multiforme (GBM)
- To assess the association of gut microbiome composition with radiation necrosis
Hypothesis: We hypothesize that stool collection and microbiome analysis taken from the time of diagnosis to disease recurrence will be feasible in Ottawa. Secondly, we hypothesize that in patients with newly diagnosed World Health Organization (WHO) Grade 4, IDH-1 R132H (Arginine to histidine mutation at site 132) wild-type glioblastoma (GBM) receiving chemoradiation (Stupp regimen), increased microbial diversity and abundance of microbiota found to be favorable in other cancers will have better survival outcomes compared to decreased gut microbial diversity and relative abundance of microbiota found to be unfavorable in other cancers
Study sample size: n=20.
This study aims to enroll a prognostically uniform population presenting with newly diagnosed GBM at a single cancer center. The primary aim of the study is to establish feasibility of conducting such a study in Ottawa.
Primary Outcome(s) The primary outcome is study feasibility. Feasibility will be determined by the following co-primary endpoints.
- Stool sample obtained at pre-radiation, post-radiation (pre-adjuvant temozolomide chemotherapy), and at time of disease relapse in ≥ 70% of enrolled patients
- Complete 15-patient (75% of target sample size) enrollment within 2 years
- Stool sample volume and quality sufficient for analysis in ≥ 75% of collected samples
Secondary Outcomes
- Overall survival (OS) and progression-free survival (PFS) in pre-defined subgroups with high gut microbial diversity and relative abundance of taxa associated with favorable outcomes in other cancers vs. low diversity and unfavorable taxa subgroup.
- Gut microbial taxonomy and diversity (i.e., microbiome make up) in late progressors versus early progressors
- Differences in gut microbiome in patients with and without post-radiation necrosis.
Timing of Standard of Care Visits and Study Procedures
Participants will be followed as part of standard of care, which involves visits at the following time points:
- Baseline: post-surgery but before temozolomide (chemo) plus radiation (pre-chemoRT)
- 3-month: approximately one month after 6 weeks of chemoradiation (post-chemoRT), but before starting maintenance phase of chemotherapy
- Months 4 to 9: monthly while on maintenance phase of chemotherapy
- Every 2-3 months after completing maintenance chemo, usually corresponding to MRI scans
There are 4-5 time points during which study participants will be asked to participate in study procedures
- Stool sample collection - 4 time points from the time of enrollment
- Baseline - pre-chemoRT
- 3 month - post-chemoRT
- 1 to 3 months after completing maintenance chemotherapy. As a result, this time point may vary (e.g., could be at 9-month mark if they finished 6 cycles of maintenance chemotherapy on schedule, but may be earlier or later, if patients stop maintenance chemo early or treatments repeatedly get delayed).
- Disease recurrence (12-week window of confirmed recurrence date)
- 7-day diet diary - 4 time points from time of enrollment.
- Baseline: pre-chemoRT
- 3-month: post-chemoRT
- 9-month: usually corresponds to after maintenance chemo
- 12 month: even further out from completion of chemo
- European Organization for Research and Treatment of Cancer (EORTC)-quality of life questionnaire (QLQ)-C30 and EORTC-QLQ-BN20 questionnaires - 5 time points from time of enrollment
- Baseline: pre-chemoRT
- 3-month: post-chemoRT
- 6-month: usually mid-maintenance chemo
- 9-month: usually corresponds to after maintenance chemo
- 12-month: even further out from completion of chemo
- Conditions
- Glioblastoma, IDH-wildtype
- Keywords
- Gut microbiome, Glioblastoma multiforme
- Medical subject headings
- Glioblastoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of collecting stool samples
Feasibility is met if stool samples obtained at pre-radiation, post-radiation (pre-adjuvant temozolomide chemotherapy), and at time of disease relapse in ≥ 70% of enrolled patients
Measured: 2 years
Feasibility of participant enrollment
Feasibility is met if 15 participants (75% of target sample size) are enrolled within 2 years
Measured: 2 years
Feasibility of stool sample analysis
Feasibility is met if 16S RNA analysis is feasible in ≥ 75% of collected stool samples
Measured: 2 years
Secondary outcomes (3)
Progression-free survival in favourable and unfavourable gut microbiota subgroups
Favourable and unfavourable gut microbiota subgroups will be pre-defined by gut microbial diversity (high vs. low) and relative abundance of taxa associated with favorable and unfavorable outcomes seen in other cancers
Measured: 5 years
Gut microbial composition in late versus early progressors
Gut microbial taxonomy and diversity (i.e., microbiome make up) in late progressors versus early progressors
Measured: 5 years
Gut microbial composition associated with radiation necrosis
Differences in gut microbiome in patients with and without post-radiation necrosis.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2022
- Study start2 Mar 2023
- Primary completionJul 2025 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma, IDH-wildtypeStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05326334
- Sponsor's protocol ID
- 3603
- Acronym
- THERABIOME-GBM
- Status last verified
- Apr 2023
- First submitted
- 2 Mar 2022
- Last updated
- 18 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- THERApeutic Outcomes Related to Gut microBIOME in Glioblastoma (GBM) Patients Receiving Chemo-radiation: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT05326334
- Acronym / sponsor ID
- THERABIOME-GBM / 3603
- Conditions
- Glioblastoma, IDH-wildtype
- Keywords
- Gut microbiome, Glioblastoma multiforme
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 2 Mar 2023 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 13 Apr 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.
This is a pilot or feasibility study to test the study plan and to find out whether enough participants will join a larger study and accept the study procedures. Eligible participants (adults with newly diagnosed glioblastoma multiforme [GBM] and had a good tumour resection [>= 70% of initial tumour volume] and plan to receive 6 weeks of chemoradiation followed by up to 6 months of chemotherapy) are asked to donate their own stool samples at 4 different time points during their treatment course. Participants will also complete a 7-day diet diary and two questionnaires about their health-related quality of life.
Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer in adults. The current best evidence-proven treatment for GBM includes maximum safe tumour resection, brain radiation over a 6-week period given with chemotherapy pills called temozolomide (Brand name: Temodal or Temodar), followed by approximately 6 months / cycles of temozolomide. Despite these treatments, the average life expectancy is generally less than 2 years.
Researchers are recognizing that the immune system has an important role in directing the effectiveness of chemotherapy, radiation, and newer therapies such as immunotherapies. Some immunotherapies have been quite successful in improving cancer control and survival in other cancers like melanoma (an aggressive skin cancer), but when these drugs were given to patients with GBM, there appeared to only be a small effect. Therefore, finding ways to make existing and new treatments work better should be a priority. Recent scientific studies have shown that the bacteria that make up our stool, often referred to as the gut microbiome, play a major role in regulating the immune system. For example, researchers were able to make patients with melanoma who previously did not respond to immunotherapy become responsive to the treatment after receiving a stool transplant from responders to immunotherapy. This provides proof of concept that we could modify the body's immune environment to favour cancer killing by changing a person's gut bacteria environment.
The role of the gut bacteria in patients with brain cancer is poorly understood as very few studies have been published about it in this population. We believe that understanding the composition of the gut microbiome and how it relates to the effectiveness and side effects of treatments in GBM patients will be an important first step to understanding how we can modify the gut microbiome to improve outcomes for patients living with GBM.
Detailed description
This is a prospective observational study designed to assess changes in the gut microbial composition and diversity in prospectively collected stool samples at important time points throughout GBM treatment and surveillance and to correlate that with patient survival outcomes and radiation necrosis.
Objectives:
- To assess feasibility of stool sample collection, banking, and analysis throughout the treatment course of GBM patients.
- To determine the association of gut microbiome composition with survival outcomes in isocitrate dehydrogenase (IDH) type 1 wild type glioblastoma multiforme (GBM)
- To assess the association of gut microbiome composition with radiation necrosis
Hypothesis: We hypothesize that stool collection and microbiome analysis taken from the time of diagnosis to disease recurrence will be feasible in Ottawa. Secondly, we hypothesize that in patients with newly diagnosed World Health Organization (WHO) Grade 4, IDH-1 R132H (Arginine to histidine mutation at site 132) wild-type glioblastoma (GBM) receiving chemoradiation (Stupp regimen), increased microbial diversity and abundance of microbiota found to be favorable in other cancers will have better survival outcomes compared to decreased gut microbial diversity and relative abundance of microbiota found to be unfavorable in other cancers
Study sample size: n=20.
This study aims to enroll a prognostically uniform population presenting with newly diagnosed GBM at a single cancer center. The primary aim of the study is to establish feasibility of conducting such a study in Ottawa.
Primary Outcome(s) The primary outcome is study feasibility. Feasibility will be determined by the following co-primary endpoints.
- Stool sample obtained at pre-radiation, post-radiation (pre-adjuvant temozolomide chemotherapy), and at time of disease relapse in ≥ 70% of enrolled patients
- Complete 15-patient (75% of target sample size) enrollment within 2 years
- Stool sample volume and quality sufficient for analysis in ≥ 75% of collected samples
Secondary Outcomes
- Overall survival (OS) and progression-free survival (PFS) in pre-defined subgroups with high gut microbial diversity and relative abundance of taxa associated with favorable outcomes in other cancers vs. low diversity and unfavorable taxa subgroup.
- Gut microbial taxonomy and diversity (i.e., microbiome make up) in late progressors versus early progressors
- Differences in gut microbiome in patients with and without post-radiation necrosis.
Timing of Standard of Care Visits and Study Procedures
Participants will be followed as part of standard of care, which involves visits at the following time points:
- Baseline: post-surgery but before temozolomide (chemo) plus radiation (pre-chemoRT)
- 3-month: approximately one month after 6 weeks of chemoradiation (post-chemoRT), but before starting maintenance phase of chemotherapy
- Months 4 to 9: monthly while on maintenance phase of chemotherapy
- Every 2-3 months after completing maintenance chemo, usually corresponding to MRI scans
There are 4-5 time points during which study participants will be asked to participate in study procedures
- Stool sample collection - 4 time points from the time of enrollment
- Baseline - pre-chemoRT
- 3 month - post-chemoRT
- 1 to 3 months after completing maintenance chemotherapy. As a result, this time point may vary (e.g., could be at 9-month mark if they finished 6 cycles of maintenance chemotherapy on schedule, but may be earlier or later, if patients stop maintenance chemo early or treatments repeatedly get delayed).
- Disease recurrence (12-week window of confirmed recurrence date)
- 7-day diet diary - 4 time points from time of enrollment.
- Baseline: pre-chemoRT
- 3-month: post-chemoRT
- 9-month: usually corresponds to after maintenance chemo
- 12 month: even further out from completion of chemo
- European Organization for Research and Treatment of Cancer (EORTC)-quality of life questionnaire (QLQ)-C30 and EORTC-QLQ-BN20 questionnaires - 5 time points from time of enrollment
- Baseline: pre-chemoRT
- 3-month: post-chemoRT
- 6-month: usually mid-maintenance chemo
- 9-month: usually corresponds to after maintenance chemo
- 12-month: even further out from completion of chemo
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- IDH-1 R132H wild type WHO grade 4 glioblastoma multiforme is the most common type of primary brain cancer. This study enrolled prognostically similar patients (at least 70% tumour volume resection, ECOG PS 0-2, eligible to receive RT 60 Gy/30 fractions)
Key inclusion criteria (6 listed)
- Patients with newly diagnosed WHO grade 4 glioblastoma, IDH-1 R132H wild type
- Maximum safe resection (≥70% of initial tumor volume resected)
- Age ≥ 18
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 or ECOG 2 if on ≤ 8 mg/day of dexamethasone (or bioequivalent)
- Plan to receive 60 Gy / 30 fractions of radiation with temozolomide within 12 weeks of surgery
Key exclusion criteria (5 listed)
- Metastatic cancer or secondary cancer that could affect interpretation of primary and secondary study outcomes
- Receiving additional systemic therapy / clinical intervention for glioblastoma that would prevent a uniform treatment cohort with temozolomide and radiation x 6 weeks followed by adjuvant temozolomide 150-200 mg/m2 on days 1-5 every 28 days for up to 6 cycles.*
- Inability to collect study stool samples
- Any diagnosis or medical condition, physical and / or psychological, that the investigator feels precludes the patient from participation in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Feasibility of collecting stool samples
Time frame: 2 years
Feasibility is met if stool samples obtained at pre-radiation, post-radiation (pre-adjuvant temozolomide chemotherapy), and at time of disease relapse in ≥ 70% of enrolled patients
Feasibility of participant enrollment
Time frame: 2 years
Feasibility is met if 15 participants (75% of target sample size) are enrolled within 2 years
Feasibility of stool sample analysis
Time frame: 2 years
Feasibility is met if 16S RNA analysis is feasible in ≥ 75% of collected stool samples
3 secondary outcomes
Progression-free survival in favourable and unfavourable gut microbiota subgroups
Time frame: 5 years
Gut microbial composition in late versus early progressors
Time frame: 5 years
Gut microbial composition associated with radiation necrosis
Time frame: 2 years
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 18 Apr 2023.
- Individual participant dataSharing planned: No
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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 Glioblastoma, IDH-wildtype, run by Ottawa Hospital Research Institute at 1 site in Canada.
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 6 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 18 Apr 2023. 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 Canada. 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 Terry L. Ng, MD (613-737-7700 ext. 70170, teng@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of collecting stool samples (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Apr 2023.