Chemoradiotherapy Versus Chemotherapy for Elderly and Frail GBM Patients
ConditionGlioblastoma Multiforme
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age65+
SponsorAHS Cancer Control Alberta
About this trial
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 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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Temozolomide monotherapy
Other interventionTemozolomide (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 productChemo-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.
Treatment groups
107 Participants
are divided into 2 treatment groupsGroup A: Standard Arm: TMZ with concurrent RT (combined modality arm)Active comparator 1 intervention
Group B: Temozolomide monotherapyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Through study completion, an average of 2 years.Secondary outcomes
1
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.
Time frame
Median, 6-month, 1-year, and 2-year rates will be measured.2
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.
Time frame
From screening until one month post adjuvant treatment.3
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.
Time frame
Throughout study completion, up to 2 years.4
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.
Time frame
Throughout study completion, up to 2 years.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
AHS Cancer Control Alberta
Lead sponsor
Alberta Cancer Foundation
Collaborator
Source ClinicalTrials.gov