Ignite Creation Date:
2025-12-18 @ 9:53 AM
Ignite Modification Date:
2025-12-18 @ 9:53 AM
Study NCT ID:
NCT04765514
Status:
None
Last Update Posted:
2025-06-12 00:00:00
First Post:
2021-01-12 00:00:00
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Chemoradiotherapy Versus Biomarker-Guided Therapy for Elderly and Frail GBM Patients
Sponsor:
None
Organization:
Study Overview
Official Title:
A Randomized Controlled Trial of Chemo-Radiotherapy Versus Biomarker-Guided Therapy for Elderly and Frail Patients With Newly Diagnosed Glioblastoma
Status:
None
Status Verified Date:
2025-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 added toxicity and inconvenience of a more protracted treatment regimen.
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 50-70), a biomarker-guided approach to therapy results in non-inferior overall survival compared to combined TMZ/RT.
Specifically, biomarker-guided therapy will consist of TMZ monotherapy for patients with a methylated MGMT promoter, and hypofractionated RT (40 Gy in 15 fractions) for patients with a non-methylated MGMT promoter.
It is hypothesized that biomarker-guided therapy 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 vs biomarker-guided therapy 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 vs biomarker-guided therapy
Methods:
Patients will be randomized to two treatment groups in a 1:1 ratio. Standard Arm: TMZ with concurrent RT (combined modality arm) Patients will receive 15 days of TMZ daily with concurrent RT. TMZ will be delivered at a dose of 75 mg/m2, given daily with RT. TMZ will be administered 1 hour before each session of RT.
After a 4-week break, patients will receive six cycles of 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.
Investigational Arm: Biomarker based treatment MGMT (+): TMZ monotherapy Patients will receive TMZ at a dose of 75 mg/m2 daily for 15 days on weekdays (Monday through Friday). This will be followed by six cycles of TMZ according to the standard 5-day schedule (days 1-5) every 28 days. 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. Dose will be determined using the body surface area (BSA) calculation.
MGMT methylation (-): No TMZ will be given. Participants will receive radiation treatment with 40Gy / 15 fractions over a period of 21 days (3 weeks).
Upon treatment completion, participants will be followed by every 3 months for 2 years and every 6 months for years 3-5. Response and progression will be evaluated using the new international criteria proposed by the Response Assessment in Neuro-Oncology working group (RANO).
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 50-70), a biomarker-guided approach to therapy results in non-inferior overall survival compared to combined TMZ/RT.
Specifically, biomarker-guided therapy will consist of TMZ monotherapy for patients with a methylated MGMT promoter, and hypofractionated RT (40 Gy in 15 fractions) for patients with a non-methylated MGMT promoter.
It is hypothesized that biomarker-guided therapy 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 vs biomarker-guided therapy 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 vs biomarker-guided therapy
Methods:
Patients will be randomized to two treatment groups in a 1:1 ratio. Standard Arm: TMZ with concurrent RT (combined modality arm) Patients will receive 15 days of TMZ daily with concurrent RT. TMZ will be delivered at a dose of 75 mg/m2, given daily with RT. TMZ will be administered 1 hour before each session of RT.
After a 4-week break, patients will receive six cycles of 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.
Investigational Arm: Biomarker based treatment MGMT (+): TMZ monotherapy Patients will receive TMZ at a dose of 75 mg/m2 daily for 15 days on weekdays (Monday through Friday). This will be followed by six cycles of TMZ according to the standard 5-day schedule (days 1-5) every 28 days. 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. Dose will be determined using the body surface area (BSA) calculation.
MGMT methylation (-): No TMZ will be given. Participants will receive radiation treatment with 40Gy / 15 fractions over a period of 21 days (3 weeks).
Upon treatment completion, participants will be followed by every 3 months for 2 years and every 6 months for years 3-5. Response and progression will be evaluated using the new international criteria proposed by the Response Assessment in Neuro-Oncology working group (RANO).
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: