GlioblastomaPhase 2NCT03506139
Biologically-based Target Volumes to Treat Newly Diagnosed Glioblastoma
A Phase 2 study testing External beam radiation therapy in people with Glioblastoma and Glioblastoma Multiforme, run by John M. Buatti at 1 site in United States.
Trial summary
This clinical trial increases radiation to areas of the brain considered to be at risk for cancer. The at-risk areas are identified by a biological MRI scan. The study will look at side effects of the radiation and overall survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- External beam radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2019to 31 Dec 2026
- Phase
- Phase 2
- 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
Who may be able to join
- Ability to understand and willingness to provide informed consent
- Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma.
- Patients must be 18 years of age or older.≥
- Karnofsky performance status ≥ 70
- Minimal life expectancy of 12 weeks.
- Maximal contiguous volume of tumor based on high b-value diffusion MRI and perfusion MRI < 1/3 volume of brain
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- Patients must be treated within 6 weeks of most recent resection
- Within 21 days of radiation fraction 1, the following blood test parameters must be met:
- Hemoglobin ≥ 10 g/dL (transfusion is acceptable)
- absolute neutrophils ≥ 1500/mm3
- platelet count ≥ 100,000/mm3
- total bilirubin ≤ 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome)
- ALT and AST ≤ 5 x ULN
- serum creatinine ≤ 2.0 mg/dL
Who cannot join
- Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is >3 years.
- Evidence of CSF dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination).
- Multifocal disease (>1 lobe of involvement) of discontiguous, contrast enhancing disease as seen on conventional MRI
- Evidence of severe concurrent disease requiring treatment
- Known active malignancy as determined by treating medical and radiation oncologist
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- Patients unable to undergo MRI exams
- Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring inpatient hospitalization or delay treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise subject safety.
- Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a Class D agent with the potential for teratogenic or abortifacient effects.
- Nursing mothers declining to discontinue breastfeeding are excluded because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide.
- Patients with reproductive potential declining to use an effective contraceptive method during treatment are excluded from this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Department of Radiation Oncology
Iowa City, Iowa, 52242
About this study
Official title: Phase II Study of High Dose Radiotherapy and Concurrent Temozolomide Using Biologically-based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma
This clinical trial increases radiation to areas of the brain considered to be at risk for cancer. The at-risk areas are identified by a biological MRI scan. The study will look at side effects of the radiation and overall survival.
Read the detailed description
This study evaluates if increasing radiation dose to at-risk areas impacts overall survival without causing a decrease in quality of life or an increase in radiation side effects.
Standard radiation dose for glioblastoma (GBM) is 60 Gray in 30 fractions, with patients receiving 1 fraction per day, Monday through Friday.
This trial will use a total of 75 Gray in 30 fractions, with participants receiving 1 fraction per day, Monday through Friday. Participants will still receive the standard chemotherapy (temozolomide) at the standard dose (75 mg/m2, once daily, 7 days a week).
This study also uses a different imaging technique to identify the tumor target and the tissues at risk. Normal imaging techniques will be used to define the standard target volume and will receive the standard radiation dose (60 Gray). A special MRI sequence will identify at risk areas based on diffusion and perfusion abnormalities. This area will receive the higher radiation dose (75 Gray).
Participants will also be asked to complete quality of life questionnaires and neurocognitive evaluations at specific time points. This is to identify any side effects from the higher radiation dose. Preliminary work done at University of Michigan suggests a lack of side effects from the higher dose of radiation.
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Being tested
- External beam radiation therapy
- Keywords
- Radiotherapy, Magnetic Resonance Imaging
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External beam radiation therapyRadiation
Also called radiotherapy, radiation
Radiotherapy to 75 Gy Radiation delivered 1 fraction / day, Monday through Friday, for a total of 30 fractions
| Study group | Role | What they receive |
|---|---|---|
| Radiation Therapy | Experimental | External beam radiation therapy delivered to target volume. Receives: Radiation: External beam radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Estimate 12-month overall survival of GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.
Measured: 12 months after completing radiation therapy
Secondary outcomes (4)
Progression free survival (PFS)
Estimate progression-free survival (PFS) in GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.
Measured: Every 2 months, for up to 60 months after completing radiation therapy, until progression or death from any cause
Identifying tissue at risk of recurrence
Assess the ability of pre-treatment and mid-treatment advanced MRI to determine areas at high risk of recurrence
Measured: 12 months after completing radiation therapy
Distinguish progression from pseudoprogression
Assess the ability of post-treatment advanced MRI to distinguish progression from pseudoprogression
Measured: 12 months after completing radiation therapy
Adverse events related to treatment
Provide descriptive data regarding health-related quality of life (QOL), symptoms and neurocognitive function
Measured: Weekly during radiation therapy, every 2 months post-radiation therapy for 7 months, then 13 & 19 months post-radiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2018
- Study start15 May 2019
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2026 (estimated)
Why it stopped: Not funded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- Group treated to 75 Gray of radiation to at-risk target
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- John M. Buatti
- Sponsor type
- University, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center
- Responsible party
- Sponsor-investigator, John M. Buatti, University of Iowa
- Investigators
- John M. Buatti, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03506139
- Sponsor's protocol ID
- 201801819
- Status last verified
- Sep 2020
- First submitted
- 12 Apr 2018
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Deidentified Individual participant data will be shared with a signed usage agreement. Additionally, a contract will be required between University of Iowa and the receiving institution.
Publications
Hamstra DA, Galban CJ, Meyer CR, Johnson TD, Sundgren PC, Tsien C, Lawrence TS, Junck L, Ross DJ, Rehemtulla A, Ross BD, Chenevert TL. Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. J Clin Oncol. 2008 Jul 10;26(20):3387-94. doi: 10.1200/JCO.2007.15.2363. Epub 2008 Jun 9.
PubMed 18541899Galban CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, Junck L, Sundgren PC, Johnson TD, Galban S, Sebolt-Leopold JS, Rehemtulla A, Ross BD. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 2011 Jul 15;17(14):4751-60. doi: 10.1158/1078-0432.CCR-10-2098. Epub 2011 Apr 28.
PubMed 21527563
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of High Dose Radiotherapy and Concurrent Temozolomide Using Biologically-based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT03506139
- Acronym / sponsor ID
- 201801819
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Keywords
- Radiotherapy, Magnetic Resonance Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not funded
- Enrolment
- 0 participants (actual)
- Lead sponsor
- John M. BuattiUniversity, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center
- Study start
- 15 May 2019 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Apr 2018 (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.
This clinical trial increases radiation to areas of the brain considered to be at risk for cancer. The at-risk areas are identified by a biological MRI scan. The study will look at side effects of the radiation and overall survival.
Detailed description
This study evaluates if increasing radiation dose to at-risk areas impacts overall survival without causing a decrease in quality of life or an increase in radiation side effects.
Standard radiation dose for glioblastoma (GBM) is 60 Gray in 30 fractions, with patients receiving 1 fraction per day, Monday through Friday.
This trial will use a total of 75 Gray in 30 fractions, with participants receiving 1 fraction per day, Monday through Friday. Participants will still receive the standard chemotherapy (temozolomide) at the standard dose (75 mg/m2, once daily, 7 days a week).
This study also uses a different imaging technique to identify the tumor target and the tissues at risk. Normal imaging techniques will be used to define the standard target volume and will receive the standard radiation dose (60 Gray). A special MRI sequence will identify at risk areas based on diffusion and perfusion abnormalities. This area will receive the higher radiation dose (75 Gray).
Participants will also be asked to complete quality of life questionnaires and neurocognitive evaluations at specific time points. This is to identify any side effects from the higher radiation dose. Preliminary work done at University of Michigan suggests a lack of side effects from the higher dose of radiation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Group treated to 75 Gray of radiation to at-risk target
| Arm | Type | Receives |
|---|---|---|
| Radiation Therapy | Experimental | Radiation: External beam radiation therapyExternal beam radiation therapy delivered to target volume. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Ability to understand and willingness to provide informed consent
- Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma.
- Patients must be 18 years of age or older.≥
- Karnofsky performance status ≥ 70
- Minimal life expectancy of 12 weeks.
Key exclusion criteria (12 listed)
- Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is >3 years.
- Evidence of CSF dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination).
- Multifocal disease (>1 lobe of involvement) of discontiguous, contrast enhancing disease as seen on conventional MRI
- Evidence of severe concurrent disease requiring treatment
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 |
|---|---|---|
| External beam radiation therapyAlso: radiotherapy, radiationRadiotherapy to 75 Gy Radiation delivered 1 fraction / day, Monday through Friday, for a total of 30 fractions | Radiation | Radiation Therapy |
Primary outcome
Overall survival
Time frame: 12 months after completing radiation therapy
Estimate 12-month overall survival of GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.
4 secondary outcomes
Progression free survival (PFS)
Time frame: Every 2 months, for up to 60 months after completing radiation therapy, until progression or death from any cause
Identifying tissue at risk of recurrence
Time frame: 12 months after completing radiation therapy
Distinguish progression from pseudoprogression
Time frame: 12 months after completing radiation therapy
Adverse events related to treatment
Time frame: Weekly during radiation therapy, every 2 months post-radiation therapy for 7 months, then 13 & 19 months post-radiation
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 9 Sep 2020.
- Background: PubMed 18541899Hamstra DA, Galban CJ, Meyer CR, Johnson TD, Sundgren PC, Tsien C, Lawrence TS, Junck L, Ross DJ, Rehemtulla A, Ross BD, Chenevert TL. Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. J Clin Oncol. 2008 Jul 10;26(20):3387-94. doi: 10.1200/JCO.2007.15.2363. Epub 2008 Jun 9.
- Background: PubMed 21527563Galban CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, Junck L, Sundgren PC, Johnson TD, Galban S, Sebolt-Leopold JS, Rehemtulla A, Ross BD. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 2011 Jul 15;17(14):4751-60. doi: 10.1158/1078-0432.CCR-10-2098. Epub 2011 Apr 28.
- Individual participant dataSharing planned: Yes. Deidentified Individual participant data will be shared with a signed usage agreement. Additionally, a contract will be required between University of Iowa and the receiving institution.
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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.
John M. Buatti, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing External beam radiation therapy in people with Glioblastoma and Glioblastoma Multiforme, run by John M. Buatti at 1 site in United States.
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 14 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: withdrawn, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
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: 12 months after completing radiation therapy). 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 NCT03506139, which also lists 2 linked publications.
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 9 Sep 2020.