6 Months Adjuvant Temozolomide (TMZ) vs No Adjuvant TMZ in Newly Diagnosed MGMT Methylated Glioblastoma (GBM)
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|ClinicalTrials.gov Identifier: NCT04926168|
Recruitment Status : Not yet recruiting
First Posted : June 15, 2021
Last Update Posted : September 10, 2021
The primary objective of this trial is to evaluate overall survival of patients with O-methylguanine-DNA methyltransferase (MGMT) methylated glioblastoma treated with or without six months of adjuvant TMZ after standard radiation (6000 centigray (cGy)) plus concurrent Temozolomide (TMZ).
Secondary Objectives include to prospectively assess the overall adverse event profile in the two treatment arms. To compare lymphocyte counts overtime between the two treatment arms and to prospectively compare quality of life in the two treatment arms as assessed by MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Neurological quality of Life/minimal infecting dose (NeuroQoL) (MID). The study will also compare progression-free survival between the two treatment arms.
|Condition or disease||Intervention/treatment|
|MGMT-Methylated Glioblastoma||Other: Delay of TMZ Other: Standard of Care (SOC) Adjuvant TMZ (no intervention|
Recent phase III trials in patients with newly diagnosed patients with glioblastoma have demonstrated that adding new agents (such as cilengitide, bevacizumab, or nivolumab) to standard radiation and TMZ do not improve survival in this disease. The modest effects on survival observed with the Optune® device are offset by the high costs, inconvenience, and impact on the social interactions of patients wearing this device. Unfortunately, there are currently no novel therapies poised to displace the European Organization Research & Treatment Cancer (EORTC) regimen as the standard of care for patients with newly diagnosed Glioblastoma Multiforme (GBM).As a result, a formal evaluation of the efficacy of the 6 months of adjuvant TMZ in this regimen is important to patients and research studies.
This is of particular importance in the 40% of patients who have MGMT methylated glioblastoma. The very small benefit observed in MGMT unmethylated patients has led investigators in Europe and the United States of America (including Cancer Therapy Evaluation Program (CTEP) sponsored studies) to approve clinical trials in MGMT unmethylated patients with newly diagnosed glioblastoma that entirely omit TMZ in both the concurrent and the adjuvant settings Given the marginal value of TMZ in the MGMT unmethylated patient population, the investigator's propose to study the value of adjuvant TMZ in the subset of the MGMT methylated population. If omitting adjuvant TMZ is not detrimental to outcomes in the methylated population then it is extremely unlikely to benefit the unmethylated population where TMZ has even less effect.
Therefore, exploring the value of the six months of adjuvant TMZ in patients with newly diagnosed MGMT methylated glioblastoma is important. If this was shown to be of minimal value in prolonging survival there would be an immediate impact on both the standard care of patients and research efforts to improve therapeutic outcomes.
|Study Type :||Observational|
|Estimated Enrollment :||120 participants|
|Official Title:||Randomized Pilot Study of Six Months Adjuvant Temozolomide (TMZ) vs No Adjuvant TMZ in Patients With Newly Diagnosed MGMT Methylated Glioblastoma (GBM) Following Standard Concurrent Radiation and TMZ|
|Estimated Study Start Date :||December 1, 2021|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Adjuvant TMZ (Treatment group):
Adjuvant TMZ (temozolomide) will be given to patients as standard of Care (SOC) treatment is administered on an outpatient basis.
Patients will be provided with medication diaries and instructed in their use. TMZ will be dispensed as SOC.
Other: Standard of Care (SOC) Adjuvant TMZ (no intervention
SOC in Adjuvant Setting no intervention
Delay TMZ (Observation group):
Patients in this cohort will have their TMZ in the adjuvant setting delayed and they will be observed with SOC procedures. Once the patient recurs, will be off "observation" and will be able to either have TMZ prescribed or something other.
Other: Delay of TMZ
Delay of TMZ to analyze the current standard of care practice of prescribing TMZ post combination (RT and TMZ).
- Overall Survival [ Time Frame: Up to 2 years ]Compare overall survival with patients receiving adjuvant TMZ to those having TMZ delayed
- Grade 3 or above adverse events [ Time Frame: 6 months ]Number of grade 3 or above adverse events
- Change in Lymphocyte count [ Time Frame: Up to 1 year ]Lymphocyte counts will be collected at baseline and every two months per standard care. Minimum measurements will be made three times through the course of trial, at baseline, 2 months from baseline measure, and a later measurement at 6 month or after. Linear mixed model will be carried out to compare the longitudinal profile of lymphocyte counts between the two arms.
- Change in Quality of life as assessed by MDASI-BT [ Time Frame: Up to 6 months ]A minimum of two reports are required for each patient, one at the baseline and another at time of first disease progression. Effort will be given to obtain the report at each standard clinical visit during the first 6 months (about 3 reports after enrollment). All MDASI-BT items are rated on numeric 0-to-10 scales, a low score indicates higher function.
- Change in Quality of life as assessed by NeuroQoL/MID. [ Time Frame: Up to 6 months ]A minimum of two reports are required for each patient, one at the baseline and another at time of first disease progression. Effort will be given to obtain the report at each standard clinical visit during the first 6 months (about 3 reports after enrollment). NeuroQoL/MID items are rated on numeric 0-to-10 scales, a low score indicates higher function.
- Progression-free survival [ Time Frame: Up to 2 years ]Time of progression-free survival is defined as date from randomization to date of progression as documented by treating physician
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04926168
|Contact: Michaella Iacoboni, RNfirstname.lastname@example.org|
|Contact: Tamara Dobson-Brown, BSemail@example.com|
|United States, Maryland|
|University of Maryland|
|Baltimore, Maryland, United States, 21201|
|Contact: Mark Mishra, MD 410-369-5237 firstname.lastname@example.org|
|Principal Investigator: Mark Mishra, MD|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157|
|Contact: Clinical Trials Office 336-713-6771|
|Contact: Roy Strowd 336-716-2357|
|Principal Investigator: Roy Strowd, MD|
|Study Chair:||Stuart Grossman, MD||Johns Hopkins University|