Recurrent GlioblastomaNCT03557372
Mathematical Model-Adapted Radiation In Glioblastoma
A study testing Mathematical Model-Adapted Radiation Fractionation Schedule in people with Recurrent Glioblastoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is studying a new schedule of radiation therapy for recurrent glioblastoma as a possible treatment for this diagnosis. This radiation schedule is based on a new model for radiation resistance in glioblastoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma
- What is being tested?
- Mathematical Model-Adapted Radiation Fractionation Schedule
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Nov 2018to 9 Nov 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Participants must have recurrent glioblastoma (WHO Grade IV), as defined on brain imaging with CT or MRI, after prior receipt of definitive therapy including neurosurgical biopsy or resection and radiation therapy with or without systemic therapy.
- Participants must be deemed appropriate candidates for re-irradiation
- Histopathologic confirmation of disease as part of routine clinical care is required either at the time of initial diagnosis and/or at the time of recurrent disease. There is no requirement for central pathologic review.
- Age ≥ 18 years at the time of enrollment
- Karnofsky Performance Status (KPS) of at least 70
Who cannot join
- Participants who have received more than one prior course of radiotherapy to the local site of progressive disease
- Participants who have received prior radiotherapy to the local site of progressive disease within < 3 months of the anticipated start of re-irradiation
- Participants with recurrent tumor extensively abutting or involving the optic structures or brainstem, as assessed by the treating radiation oncologist
- Participants without a definable tumor cavity on MRI or CT obtained at study enrollment
- Participants receiving concurrent cytotoxic chemotherapy (i.e. temozolomide, CCNU, vincristine, procarbazine) or concurrent immunotherapy (i.e. pembrolizumab, nivolumab); however, participants may receive sequential chemotherapy before or after radiation without limitation. Participants may receive concurrent corticosteroid and/or anti-angiogenic therapy (i.e. bevacizumab) if clinically indicated.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Mathematical Model-Adapted Radiation Fractionation Schedule for Patients With Recurrent Glioblastoma (MARS-Glio)
This research study is studying a new schedule of radiation therapy for recurrent glioblastoma as a possible treatment for this diagnosis. This radiation schedule is based on a new model for radiation resistance in glioblastoma.
The name of the radiation schedule involved in this study is:
- Re-irradiation for glioblastoma using a novel Mathematical Model-Adapted Radiation Fractionation Schedule
Read the detailed description
This research study is a Feasibility Study, which means that this is the first time that investigators are examining this new radiation schedule for recurrent glioblastoma.
- The FDA (the U.S. Food and Drug Administration) has approved radiation therapy as a treatment option for your disease.
- This is the first time that this particular radiation schedule will be tested in humans. There many other studies which have tested different radiation schedules in glioblastoma.
In this research study, investigators are adapting a standard two-week schedule of radiation commonly used for recurrent glioblastoma using a mathematical model. This study uses the same total dose of radiation as standard treatments but breaks up the dose into different amounts daily to maximize tumor kill. investigators have used a new mathematical model to create this schedule of radiation. This model was created to better represent how glioblastoma cells can escape the damaging effects of radiation. Based on the results of several laboratory studies, it is possible that this model may result in improved outcomes compared to standard radiation schedules.
The primary question of this study is to see whether participants can complete this new radiation schedule at the scheduled times. In addition, investigators will follow participants to ensure that this treatment is safe. If this treatment proves feasible, investigators hope to compare this treatment directly with standard radiation schedules for newly diagnosed and recurrent glioblastoma.
- Conditions
- Recurrent Glioblastoma
- Being tested
- Mathematical Model-Adapted Radiation Fractionation Schedule
- Keywords
- Recurrent glioblastoma, Radiation Therapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mathematical Model-Adapted Radiation Fractionation ScheduleRadiation
- Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks
- Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes.
- Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Mathematical Model-Adapted Radiation | Experimental | Mathematical Model-Adapted Radiation Fractionation Schedule Receives: Radiation: Mathematical Model-Adapted Radiation Fractionation Schedule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled
Successful completion of radiotherapy is defined as receipt of all scheduled fractions of daily radiotherapy within 24 hours of once daily fractions and within 1 hour of three-times daily fractions.
Measured: 10 Days
Secondary outcomes (8)
Number of Participants With Radiation Necrosis
Radiation necrosis (RN) was defined by clinical assessment including imaging features of an expansile, centrally hypointense lesion with increasing surrounding vasogenic edema and typically without features of high grade recurrence (restricted diffusion, elevated cerebral blood volume). Symptomatic RN included patients with radiographic RN requiring intervention such as corticosteroid therapy for neurologic symptoms, headaches, or signs of elevated intracranial pressure.
Measured: 6 months
Number of Participants With Seizures
Count of number of patients developing new/worsening seizures within 6 months of receiving protocol radiation therapy
Measured: 6 months
Overall Survival (OS)
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Measured: range of follow-up from date of registration was 1.2 - 38.6 months
Grade 3-5 Treatment-related Toxicity Rate
All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.
Measured: 6 Months
Median Progression-Free Survival (PFS)
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) (defined protocol section 12.7) or death, or is censored at time of last disease assessment.
Measured: Disease evaluated on visit 4,5,6 and every 2-4 months in long-term. The range of follow-up from date of registration was 1.2 - 38.6 months and the median was 7.3 months.
Median Local Recurrence-free Survival
Local recurrence-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented Local recurrence or death, or is censored at time of last disease assessment.
Measured: Disease evaluated on visit 4,5,6 and every 2-4 months in long-term. The range of follow-up from date of registration was 1.2 - 38.6 months and the median was 7.3 months.
Number of Participants Undergoing Salvage Craniotomy
Count of patients undergoing salvage craniotomy for resection or decompression of progressively enlarging tumor within 6 months of receipt of protocol radiation therapy.
Measured: 6 Months
Number of Participants Receiving Additional Systemic Treatments After Reirradiation
Count of patients undergoing systemic therapies for presumed recurrence or progression of disease within 6 months after receipt of protocol radiation therapy
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start12 Nov 2018
- Primary completion9 Nov 2022
- Study completion9 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shyam Tanguturi, MD, Dana-Farber Cancer Institute
- Investigators
- Shyam Tanguturi, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03557372
- Sponsor's protocol ID
- 18-105
- Status last verified
- Oct 2023
- First submitted
- 23 May 2018
- Last updated
- 26 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Dean JA, Tanguturi SK, Cagney D, Shin KY, Youssef G, Aizer A, Rahman R, Hammoudeh L, Reardon D, Lee E, Dietrich J, Tamura K, Aoyagi M, Wickersham L, Wen PY, Catalano P, Haas-Kogan D, Alexander BM, Michor F. Phase I study of a novel glioblastoma radiation therapy schedule exploiting cell-state plasticity. Neuro Oncol. 2023 Jun 2;25(6):1100-1112. doi: 10.1093/neuonc/noac253.
PubMed 36402744
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mathematical Model-Adapted Radiation Fractionation Schedule for Patients With Recurrent Glioblastoma (MARS-Glio)
- ClinicalTrials.gov ID
- NCT03557372
- Acronym / sponsor ID
- 18-105
- Conditions
- Recurrent Glioblastoma
- Keywords
- Recurrent glioblastoma, Radiation Therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- 9 Nov 2022 (actual)
- Study completion
- 9 Nov 2022 (actual)
- First posted
- 15 Jun 2018 (actual)
- Results
- Posted 11 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a new schedule of radiation therapy for recurrent glioblastoma as a possible treatment for this diagnosis. This radiation schedule is based on a new model for radiation resistance in glioblastoma.
The name of the radiation schedule involved in this study is:
- Re-irradiation for glioblastoma using a novel Mathematical Model-Adapted Radiation Fractionation Schedule
Detailed description
This research study is a Feasibility Study, which means that this is the first time that investigators are examining this new radiation schedule for recurrent glioblastoma.
- The FDA (the U.S. Food and Drug Administration) has approved radiation therapy as a treatment option for your disease.
- This is the first time that this particular radiation schedule will be tested in humans. There many other studies which have tested different radiation schedules in glioblastoma.
In this research study, investigators are adapting a standard two-week schedule of radiation commonly used for recurrent glioblastoma using a mathematical model. This study uses the same total dose of radiation as standard treatments but breaks up the dose into different amounts daily to maximize tumor kill. investigators have used a new mathematical model to create this schedule of radiation. This model was created to better represent how glioblastoma cells can escape the damaging effects of radiation. Based on the results of several laboratory studies, it is possible that this model may result in improved outcomes compared to standard radiation schedules.
The primary question of this study is to see whether participants can complete this new radiation schedule at the scheduled times. In addition, investigators will follow participants to ensure that this treatment is safe. If this treatment proves feasible, investigators hope to compare this treatment directly with standard radiation schedules for newly diagnosed and recurrent glioblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mathematical Model-Adapted Radiation | Experimental | Radiation: Mathematical Model-Adapted Radiation Fractionation ScheduleMathematical Model-Adapted Radiation Fractionation Schedule |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participants must have recurrent glioblastoma (WHO Grade IV), as defined on brain imaging with CT or MRI, after prior receipt of definitive therapy including neurosurgical biopsy or resection and radiation therapy with or without systemic therapy.
- Participants must be deemed appropriate candidates for re-irradiation
- Histopathologic confirmation of disease as part of routine clinical care is required either at the time of initial diagnosis and/or at the time of recurrent disease. There is no requirement for central pathologic review.
- Age ≥ 18 years at the time of enrollment
- Karnofsky Performance Status (KPS) of at least 70
Key exclusion criteria (5 listed)
- Participants who have received more than one prior course of radiotherapy to the local site of progressive disease
- Participants who have received prior radiotherapy to the local site of progressive disease within < 3 months of the anticipated start of re-irradiation
- Participants with recurrent tumor extensively abutting or involving the optic structures or brainstem, as assessed by the treating radiation oncologist
- Participants without a definable tumor cavity on MRI or CT obtained at study enrollment
- Participants receiving concurrent cytotoxic chemotherapy (i.e. temozolomide, CCNU, vincristine, procarbazine) or concurrent immunotherapy (i.e. pembrolizumab, nivolumab); however, participants may receive sequential chemotherapy before or after radiation without limitation. Participants may receive concurrent corticosteroid and/or anti-angiogenic therapy (i.e. bevacizumab) if clinically indicated.
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 |
|---|---|---|
| Mathematical Model-Adapted Radiation Fractionation Schedule* Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks * Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. * Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment. | Radiation | Mathematical Model-Adapted Radiation |
Primary outcome
Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled
Time frame: 10 Days
Successful completion of radiotherapy is defined as receipt of all scheduled fractions of daily radiotherapy within 24 hours of once daily fractions and within 1 hour of three-times daily fractions.
8 secondary outcomes
Number of Participants With Radiation Necrosis
Time frame: 6 months
Number of Participants With Seizures
Time frame: 6 months
Overall Survival (OS)
Time frame: range of follow-up from date of registration was 1.2 - 38.6 months
Grade 3-5 Treatment-related Toxicity Rate
Time frame: 6 Months
Median Progression-Free Survival (PFS)
Time frame: Disease evaluated on visit 4,5,6 and every 2-4 months in long-term. The range of follow-up from date of registration was 1.2 - 38.6 months and the median was 7.3 months.
Median Local Recurrence-free Survival
Time frame: Disease evaluated on visit 4,5,6 and every 2-4 months in long-term. The range of follow-up from date of registration was 1.2 - 38.6 months and the median was 7.3 months.
Number of Participants Undergoing Salvage Craniotomy
Time frame: 6 Months
Number of Participants Receiving Additional Systemic Treatments After Reirradiation
Time frame: 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36402744Dean JA, Tanguturi SK, Cagney D, Shin KY, Youssef G, Aizer A, Rahman R, Hammoudeh L, Reardon D, Lee E, Dietrich J, Tamura K, Aoyagi M, Wickersham L, Wen PY, Catalano P, Haas-Kogan D, Alexander BM, Michor F. Phase I study of a novel glioblastoma radiation therapy schedule exploiting cell-state plasticity. Neuro Oncol. 2023 Jun 2;25(6):1100-1112. doi: 10.1093/neuonc/noac253.
Related trials for Recurrent Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
RecruitingObservational study
Collection of Blood and Urine Samples in Patients Receiving Radiation Therapy for Glioblastoma Multiforme
Glioblastoma Multiforme
Active, not recruitingPhase 3
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM
Glioblastoma, Recurrent Glioblastoma
RecruitingPhase 1
A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
Glioblastoma Multiforme of Brain, Glioma
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.
Shyam Tanguturi, MD principal investigator
Brigham and Women's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mathematical Model-Adapted Radiation Fractionation Schedule in people with Recurrent Glioblastoma, run by Dana-Farber Cancer Institute at 2 sites 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 5 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: finished, as of the sponsor's last update on 26 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled (time frame: 10 Days). 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 NCT03557372, which also lists 1 linked publication.
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 26 Oct 2023.