THERApeutic Outcomes Related to Gut microBIOME in Glioblastoma (GBM) Patients Receiving Chemo-radiation (THERABIOME-GBM)

NCT05326334 | Recruiting DMC

• 1 other identifier: 3603
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Glioblastoma, IDH-wildtype

Keywords

Gut microbiome; Glioblastoma multiforme

Outcome Measures

Primary Outcomes (3)

• 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

  2 years

• Feasibility of participant enrollment

  Feasibility is met if 15 participants (75% of target sample size) are enrolled within 2 years

  2 years

• Feasibility of stool sample analysis

  Feasibility is met if 16S RNA analysis is feasible in ≥ 75% of collected stool samples

  2 years

Secondary Outcomes (3)

• Progression-free survival in favourable and unfavourable gut microbiota subgroups

  5 years

• Gut microbial composition in late versus early progressors

  5 years

• Gut microbial composition associated with radiation necrosis

  2 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

This study collects patient stool samples for 16S RNA analysis.

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Terry L. Ng, MD

CONTACT

613-737-7700; teng@toh.ca

Vimoj Nair, MD

CONTACT

613-737-7700; vnair@toh.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: April 13, 2022
• Study Start: March 2, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): September 1, 2029
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)