Glioblastoma MultiformePhase 2NCT04765514

Chemoradiotherapy Versus Chemotherapy for Elderly and Frail GBM Patients

A Phase 2 study testing Temozolomide monotherapy and Chemo-Radiotherapy with concurrent temozolomide. in people with Glioblastoma Multiforme, run by AHS Cancer Control Alberta at 2 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Currently, the optimal treatment regimen for elderly Glioblastoma (GBM) patients with poor performance status (PS) is unknown. Based on data for elderly GBM patients and the limited data for patients with poor PS, hypofractionated RT or a short course of Temozolomide (TMZ) may provide survival benefit without the… Read more about this study

Who is it for?: Ages 65 years and older
Conditions the study is for: Glioblastoma Multiforme
What is being tested?: Temozolomide monotherapy and Chemo-Radiotherapy with concurrent temozolomide.
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 107 participants
Where: 2 sitesCanada
Study dates: 27 Jul 2022to Jun 2032
Phase: Phase 2
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 65 years and older
All sexes
No healthy volunteers
Older adult

Who may be able to join

Newly-diagnosed, histologically proven, intracranial glioblastoma with maximal safe resection. Biopsy alone is expected if resection is not possible. MGMT promoter methylation status must be tested and the results positive (defined as all non-negative MGMT status, including intermediate or indeterminate status (i.e., with cutoff higher than the MGMT negative threshold).
History and physical examination, including neurological examination, within 14 days prior to randomization.
Age ≥ 65 \& KPS of 60 - 70
Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization.
Laboratory evaluation within 7 days prior to randomization, with adequate function as defined below:
ANC ≥ 1.5 x 109/L

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Platelets ≥ 100 x 109/L
Serum creatinine ≤ 1.5 times ULN or estimated Glomerular Filtration Rate (eGFR) > 59
Total serum bilirubin ≤ 30 umol/L (ie ≤ 1.5 times ULN)
ALT < 150 U/L (ie < 3 times ULN)
AST < 120 U/L (ie < 3 times ULN)
Alkaline phosphatase < 390 U/L (ie < 3 times ULN)
Patients must sign a study-specific informed consent prior to study registration.
Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 6 months after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
This will apply for male patients only and their female partner if of child bearing potential.
Effective contraception should also be used by male patients taking temozolomide. Men being treated with temozolomide are advised not to father a child during or up to 6 months after discontinuation of treatment (male patients).
Male patients should agree to not donate sperm during the study treatment and for six months post treatment completion.

Who cannot join

Negative MGMT promoter methylation status, or a status of not reportable.
Recurrent malignant gliomas
Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide
Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during participation in the study.
Severe, active co-morbidity, defined as follows:

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Unstable angina and/or congestive heart failure requiring hospitalization
Transmural myocardial infarction within the last 6 months
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study registration
Any severe, active co-morbidity precluding delivery of temozolomide.
History of hypersensitivity reaction to temozolomide components or to dacarbazine.
Active HBV infection

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

Arthur J.E. Child Comprehensive Cancer Center (formerly Tom Baker Cancer Centre)
Calgary, Alberta
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2

Other trials in Canada

About this study

Official title: A Randomized Controlled Trial of Chemo-Radiotherapy Versus Chemotherapy for Elderly and Frail Patients With Newly Diagnosed Glioblastoma

In particular, treatment with RT or TMZ monotherapy on the basis of methylated O6 - methyl guanine - DNA methyltransferase (MGMT) promoter methylation status, followed by the alternative therapy at progression, may provide a safe and effective treatment regimen for patients with poor PS.

The hypothesis of this trial is that in elderly GBM patients with poor performance status (age ≥ 65 years and KPS 60-70), a chemotherapy alone (TMZ monotherapy) approach to therapy results in non-inferior overall survival compared to combined TMZ/RT.

It is hypothesized that chemotherapy will result in non-inferior progression-free survival, reduced toxicity and increased cost-effectiveness compared to combined chemoradiotherapy.

Primary objective:

To compare overall survival of standard therapy vs chemotherapy in elderly and frail patients with newly diagnosed GBM.

Secondary objective:

To evaluate progression-free survival following treatment in both arms.
To evaluate adverse events according to CTCAE criteria in both arms.
To evaluate health-related quality-of-life as assessed by MoCA and EORTC QLQ-C30/QLQ-BN20 questionnaires in both arms.
To evaluate cost-effectiveness of standard therapy vs chemotherapy

Methods:

Patients will be randomized to two treatment groups in a 1:1 ratio. Standard Arm: Combined modality arm Chemo-radiotherapy consisting of 40 Gy in 15 daily fractions with concurrent TMZ. TMZ will be delivered at a dose of 75 mg/m2 daily for 21 days. TMZ will be administered 1 hour before each session of RT.

After a 4-week break, patients will receive adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue. If tolerated, additional cycles of adjuvant TMZ may be administered at the treating investigator's discretion according to site practice.

Investigational Arm: TMZ monotherapy Patients will receive TMZ at a dose of 75 mg/m2 daily for 21 days, followed by adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue. If tolerated, additional cycles of adjuvant TMZ may be administered at the treating investigator's discretion according to site practice.

Upon treatment completion, participants will be followed by every 2 and 3 months for 2 years. Response and progression will be evaluated using the new international criteria proposed by the Response Assessment in Neuro-Oncology working group (RANO).

Conditions: Glioblastoma Multiforme
Being tested: Temozolomide monotherapy, Chemo-Radiotherapy with concurrent temozolomide.
Medical subject headings: Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Temozolomide monotherapyOther
Temozolomide (TMZ) daily for 21 days, followed by up to 6 cycles of adjuvant TMZ, as tolerated. If tolerated, additional cycles of adjuvant TMZ may be administered.
Chemo-Radiotherapy with concurrent temozolomide.Combination product
Chemo-radiotherapy consisting of 40 Gy administered in 15 fractions on weekdays (Monday - Friday) concurrently with TMZ 75 mg/m2 daily for 21 days. This will be followed by up to 6 cycles of adjuvant TMZ (150-200 mg/m2 once daily on days 1-5 of a 28 day cycle), as tolerated. If tolerated, additional cycles of adjuvant TMZ may be administered at the treating investigator's discretion.

Study groups in NCT04765514
Study group	Role	What they receive
Standard Arm: TMZ with concurrent RT (combined modality arm)	Active comparator	Patients will receive a total of 21 days of Temozolomide (TMZ), with 15 days of TMZ administered daily with concurrent RT (40 Gy in 15 fractions). TMZ will be delivered at a dose of 75 mg/m2, given daily (Monday through Friday) with RT for 15 days, at least one hour before each session of RT (or per institutional site practice). After a 4-week break, patients will receive adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue. If tolerated, additional cycles of TMZ may be administered at the treating investigator's discretion, according to institutional site practice. Receives: Combination Product: Chemo-Radiotherapy with concurrent temozolomide.
Temozolomide monotherapy	Experimental	Patients will receive Temozolomide (TMZ) at a dose of 75 mg/m2 daily for 21 consecutive days. This will be followed 4 weeks later by adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue. If tolerated, additional cycles of adjuvant TMZ may be administered at the treating investigator's discretion according to institutional site practice. Receives: Other: Temozolomide monotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall survival
Time between randomization and death due to any cause. Patients without an event will be censored the last time they were known to be alive.
Measured: Through study completion, an average of 2 years.

Secondary outcomes (6)

Progression-free survival
Time between randomization and radiographic progression based on RANO criteria or death due to any cause. Patients without an event will be censored at the date of last follow-up for progression.
Measured: Median, 6-month, 1-year, and 2-year rates will be measured.
Frequency of Adverse Events related to the treatment administered
Adverse events related to the treatment(s) administered will be recorded from screening until one month post adjuvant treatment. Adverse events will be assessed according to NCI CTCAE version 4.0 criteria.
Measured: From screening until one month post adjuvant treatment.
Health Related Quality of Life (EORTC QLQ-C30)
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Measured: Throughout study completion, up to 2 years.
Health Related Quality of Life (EORTC QLQ-BN20)
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Measured: Throughout study completion, up to 2 years.
Cost effectiveness
Assessed by the incremental cost-effectiveness ratio (ICER), calculated as: Cost per life-year gained = (Difference in direct costs between chemotherapy and chemoradiotherapy) ÷ (Difference in life-years gained between chemotherapy and chemoradiotherapy). The direct unit costs of TMZ and associated laboratory testing, RT, and costs associated with any grade 3-4 adverse events (eg hospitalization) will be included.
Measured: Upon study completion, an average of 2 years
Cognitive and mental function
Assessed by Montreal Cognitive Assessment (MoCA). This assessment was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points; a score of 26 or above is considered normal.
Measured: Throughout study completion, up to 2 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jul 2022Jun 2032

First posted21 Feb 2021
Study start27 Jul 2022
Primary completionJun 2032 (estimated)
Study completionJun 2032 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Glioblastoma MultiformeStudies 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: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 107 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04765514
Sponsor's protocol ID: IIT-0012
Status last verified: Oct 2026
First submitted: 12 Jan 2021
Last updated: 3 Nov 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Glioblastoma Multiforme trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Controlled Trial of Chemo-Radiotherapy Versus Chemotherapy for Elderly and Frail Patients With Newly Diagnosed Glioblastoma
ClinicalTrials.gov ID: NCT04765514
Acronym / sponsor ID: IIT-0012
Conditions: Glioblastoma Multiforme
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 107 participants (estimated)
Lead sponsor: AHS Cancer Control AlbertaUniversity, hospital or other
Collaborators: Alberta Cancer Foundation
Study start: 27 Jul 2022 (actual)
Primary completion: Jun 2032 (estimated)
Study completion: Jun 2032 (estimated)
First posted: 21 Feb 2021 (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.

It is hypothesized that chemotherapy will result in non-inferior progression-free survival, reduced toxicity and increased cost-effectiveness compared to combined chemoradiotherapy.

Primary objective:

To compare overall survival of standard therapy vs chemotherapy in elderly and frail patients with newly diagnosed GBM.

Secondary objective:

To evaluate progression-free survival following treatment in both arms.
To evaluate adverse events according to CTCAE criteria in both arms.
To evaluate health-related quality-of-life as assessed by MoCA and EORTC QLQ-C30/QLQ-BN20 questionnaires in both arms.
To evaluate cost-effectiveness of standard therapy vs chemotherapy

Methods:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Standard Arm: TMZ with concurrent RT (combined modality arm)	Active comparator	Combination Product: Chemo-Radiotherapy with concurrent temozolomide.Patients will receive a total of 21 days of Temozolomide (TMZ), with 15 days of TMZ administered daily with concurrent RT (40 Gy in 15 fractions). TMZ will be delivered at a dose of 75 mg/m2, given daily (Monday through Friday) with RT for 15 days, at least one hour before each session of RT (or per institutional site practice). After a 4-week break, patients will receive adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue. If tolerated, additional cycles of TMZ may be administered at the treating investigator's discretion, according to institutional site practice.
Temozolomide monotherapy	Experimental	Other: Temozolomide monotherapyPatients will receive Temozolomide (TMZ) at a dose of 75 mg/m2 daily for 21 consecutive days. This will be followed 4 weeks later by adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue. If tolerated, additional cycles of adjuvant TMZ may be administered at the treating investigator's discretion according to institutional site practice.

Who may qualify

Ages: 65 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (18 listed)

Newly-diagnosed, histologically proven, intracranial glioblastoma with maximal safe resection. Biopsy alone is expected if resection is not possible. MGMT promoter methylation status must be tested and the results positive (defined as all non-negative MGMT status, including intermediate or indeterminate status (i.e., with cutoff higher than the MGMT negative threshold).
History and physical examination, including neurological examination, within 14 days prior to randomization.
Age ≥ 65 \& KPS of 60 - 70
Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization.
Laboratory evaluation within 7 days prior to randomization, with adequate function as defined below:

Key exclusion criteria (12 listed)

Negative MGMT promoter methylation status, or a status of not reportable.
Recurrent malignant gliomas
Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide
Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during 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.

Interventions

Intervention	Type	Arms
Temozolomide monotherapyTemozolomide (TMZ) daily for 21 days, followed by up to 6 cycles of adjuvant TMZ, as tolerated. If tolerated, additional cycles of adjuvant TMZ may be administered.	Other	Temozolomide monotherapy
Chemo-Radiotherapy with concurrent temozolomide.Chemo-radiotherapy consisting of 40 Gy administered in 15 fractions on weekdays (Monday - Friday) concurrently with TMZ 75 mg/m2 daily for 21 days. This will be followed by up to 6 cycles of adjuvant TMZ (150-200 mg/m2 once daily on days 1-5 of a 28 day cycle), as tolerated. If tolerated, additional cycles of adjuvant TMZ may be administered at the treating investigator's discretion.	Combination product	Standard Arm: TMZ with concurrent RT (combined modality arm)

Primary outcome

Overall survival
Time frame: Through study completion, an average of 2 years.
Time between randomization and death due to any cause. Patients without an event will be censored the last time they were known to be alive.

6 secondary outcomes

Progression-free survival
Time frame: Median, 6-month, 1-year, and 2-year rates will be measured.
Frequency of Adverse Events related to the treatment administered
Time frame: From screening until one month post adjuvant treatment.
Health Related Quality of Life (EORTC QLQ-C30)
Time frame: Throughout study completion, up to 2 years.
Health Related Quality of Life (EORTC QLQ-BN20)
Time frame: Throughout study completion, up to 2 years.
Cost effectiveness
Time frame: Upon study completion, an average of 2 years
Cognitive and mental function
Time frame: Throughout study completion, up to 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 3 Nov 2026.
Individual participant dataSharing planned: No

Related trials for Glioblastoma Multiforme

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
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Glioblastoma
RecruitingPhase 1/2
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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. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Temozolomide monotherapy and Chemo-Radiotherapy with concurrent temozolomide. in people with Glioblastoma Multiforme, run by AHS Cancer Control Alberta at 2 sites 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 18 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: Through study completion, an average of 2 years.). 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 NCT04765514.

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 3 Nov 2026.