MGMT-Methylated GlioblastomaNCT04926168
6 Months Adjuvant Temozolomide (TMZ) vs No Adjuvant TMZ in Newly Diagnosed MGMT Methylated Glioblastoma (GBM)
An observational study of MGMT-Methylated Glioblastoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Trial summary
The primary objective of this trial is to evaluate overall survival of patients with O[6]-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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MGMT-Methylated Glioblastoma
- What is being tested?
- Delay of TMZ
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2023to 31 Dec 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients who have completed 6weeks of TMZ + RT and have had good performance in that setting are eligible to be enrolled in this study to observe outcomes from being randomized to receive Standard of Care Adjuvant TMZ (6months TMZ 5 Days 1-5 or each cycle) or delay of adjuvant TMZ until recurrence post TMZ and RT. At recurrence patient may choose to start TMZ or some other treatment.
Who may be able to join
- Patients must be 18 years of age or older.
- Patients must have a Karnofsky Performance Status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).
- Patients must have had a pathologically confirmed recently diagnosed primary glioblastoma before they began concurrent radiation and temozolomide.
- Patients must have tumor MGMT methylation status of methylated using a Clinical Laboratory Improvement Amendments (CLIA)-approved diagnostic test. Results of routinely-used methods for MGMT methylation testing (e.g. Mutagenically separated- polymerase chain reaction (MS-PCR) or quantitative PCR) are acceptable.
- Documented mutated isocitrate dehydrogenase 1 gene (IDH1) isocitrate dehydrogenase 1 gene (IDH2)status: patients with either wild-type or(IDH) status are eligible. Patients with no documented status are also eligible and the status should be listed as unknown.
- Patients must be completing or have completed 6 weeks of standard concurrent RT/TMZ.
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- Patients' post-operative treatment must have included at least 80% of standard radiation and concomitant temozolomide. Patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes (TIL), lymphokine activated killer cells (LAK) or gene therapy), or hormonal therapy for their brain tumor. Prior Gliadel Wafers are allowed. Glucocorticoid therapy is allowed.
- Patients must be clinically eligible for the six months of adjuvant temozolomide.
- Patients must be able to provide written informed consent.
- Patients must have baseline MRI performed within the 21 days prior to starting entering the "adjuvant" treatment or observation period.
- Patients must have the following organ and marrow functions:
- Absolute neutrophil count ≥1,500/µL Platelets ≥100,000/µL Hemoglobin ≥ 9 g/dL Total bilirubin ≤1.5 × institutional upper limit of normal (ULN), (except for patients with known Gilbert's syndrome who must have normal direct bilirubin) aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 × ULN Creatinine ≤1.5 × ULN OR Creatinine clearance ≥ 60 mL/min/1.73m2
Who cannot join
- Patients receiving any other standard or investigational agents or who plan to use the OPTUNE device or other therapies for the glioblastoma are ineligible.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible.
- Patients must not have received prior RT, chemotherapy (except for their concurrent radiation and temozolomide for their recently diagnosed glioblastoma), immunotherapy or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor. Corticosteroid therapy is allowed.
- Patients must not have had a prior diagnosis of a lower grade glioma.
- No active treatment for other cancers in the past 3 years.
About this study
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
The primary objective of this trial is to evaluate overall survival of patients with O[6]-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.
Read the detailed description
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.
- Conditions
- MGMT-Methylated Glioblastoma
- Being tested
- Delay of TMZ, Standard of Care (SOC) Adjuvant TMZ (no intervention
- Keywords
- TMZ, MGMT, adjuvant TMZ, GBM, Newly Diagnosed
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delay of TMZOther
Delay of TMZ to analyze the current standard of care practice of prescribing TMZ post combination (RT and TMZ).
Standard of Care (SOC) Adjuvant TMZ (no interventionOther
SOC in Adjuvant Setting no intervention
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Standard of Care (SOC) Adjuvant TMZ (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. Receives: Other: Delay of TMZ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Compare overall survival with patients receiving adjuvant TMZ to those having TMZ delayed
Measured: Up to 2 years
Secondary outcomes (5)
Grade 3 or above adverse events
Number of grade 3 or above adverse events
Measured: 6 months
Change in Lymphocyte count
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.
Measured: Up to 1 year
Change in Quality of life as assessed by MDASI-BT
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.
Measured: Up to 6 months
Change in Quality of life as assessed by NeuroQoL/MID.
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.
Measured: Up to 6 months
Progression-free survival
Time of progression-free survival is defined as date from randomization to date of progression as documented by treating physician
Measured: 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.
- First posted15 Jun 2021
- Study start1 Mar 2023 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Why it stopped: lack of funds
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MGMT-Methylated GlioblastomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stuart Grossman, MD, Study chair, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04926168
- Sponsor's protocol ID
- ABTCv2-2101
- Other IDs
- IRB00285623
- Status last verified
- Aug 2022
- First submitted
- 8 Jun 2021
- Last updated
- 10 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04926168
- Acronym / sponsor ID
- ABTCv2-2101
- Conditions
- MGMT-Methylated Glioblastoma
- Keywords
- TMZ, MGMT, adjuvant TMZ, GBM, Newly Diagnosed
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: lack of funds
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- 1 Mar 2023 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 15 Jun 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.
The primary objective of this trial is to evaluate overall survival of patients with O[6]-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.
Detailed description
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adjuvant TMZ (Treatment group): | – | Other: Standard of Care (SOC) Adjuvant TMZ (no interventionAdjuvant 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. |
| Delay TMZ (Observation group): | – | Other: Delay of TMZPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients who have completed 6weeks of TMZ + RT and have had good performance in that setting are eligible to be enrolled in this study to observe outcomes from being randomized to receive Standard of Care Adjuvant TMZ (6months TMZ 5 Days 1-5 or each cycle) or delay of adjuvant TMZ until recurrence post TMZ and RT. At recurrence patient may choose to start TMZ or some other treatment.
Key inclusion criteria (12 listed)
- Patients must be 18 years of age or older.
- Patients must have a Karnofsky Performance Status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).
- Patients must have had a pathologically confirmed recently diagnosed primary glioblastoma before they began concurrent radiation and temozolomide.
- Patients must have tumor MGMT methylation status of methylated using a Clinical Laboratory Improvement Amendments (CLIA)-approved diagnostic test. Results of routinely-used methods for MGMT methylation testing (e.g. Mutagenically separated- polymerase chain reaction (MS-PCR) or quantitative PCR) are acceptable.
- Documented mutated isocitrate dehydrogenase 1 gene (IDH1) isocitrate dehydrogenase 1 gene (IDH2)status: patients with either wild-type or(IDH) status are eligible. Patients with no documented status are also eligible and the status should be listed as unknown.
Key exclusion criteria (5 listed)
- Patients receiving any other standard or investigational agents or who plan to use the OPTUNE device or other therapies for the glioblastoma are ineligible.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible.
- Patients must not have received prior RT, chemotherapy (except for their concurrent radiation and temozolomide for their recently diagnosed glioblastoma), immunotherapy or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor. Corticosteroid therapy is allowed.
- Patients must not have had a prior diagnosis of a lower grade glioma.
- No active treatment for other cancers in the past 3 years.
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 |
|---|---|---|
| Delay of TMZDelay of TMZ to analyze the current standard of care practice of prescribing TMZ post combination (RT and TMZ). | Other | Delay TMZ (Observation group): |
| Standard of Care (SOC) Adjuvant TMZ (no interventionSOC in Adjuvant Setting no intervention | Other | Adjuvant TMZ (Treatment group): |
Primary outcome
Overall Survival
Time frame: Up to 2 years
Compare overall survival with patients receiving adjuvant TMZ to those having TMZ delayed
5 secondary outcomes
Grade 3 or above adverse events
Time frame: 6 months
Change in Lymphocyte count
Time frame: Up to 1 year
Change in Quality of life as assessed by MDASI-BT
Time frame: Up to 6 months
Change in Quality of life as assessed by NeuroQoL/MID.
Time frame: Up to 6 months
Progression-free survival
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2022.
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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.
Stuart Grossman, MD study chair
Johns Hopkins University
Questions about this trial
What is this clinical trial studying?
An observational study of MGMT-Methylated Glioblastoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
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 12 inclusion and 5 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: withdrawn, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Aug 2022.