Spectroscopic MRI, Proton Therapy, and Avastin for Recurrent Glioblastoma
Pilot Trial of Spectroscopic MRI-guided, Dose-Escalated Proton Radiation Therapy and Bevacizumab for Recurrent Glioblastoma
1 other identifier
interventional
96
1 country
1
Brief Summary
The purpose of this research is to find hidden cancer with an experimental magnetic resonance imaging (MRI) scan called spectroscopic magnetic resonance imaging (sMRI). That spectroscopic MRI scan will be used to increase the area of the brain receiving radiation and then the dose of radiation in attempt to kill more of the cancer. Proton radiotherapy and bevacizumab (Avastin) are used to minimize the possible side effects of this approach.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Sep 2022
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 22, 2022
CompletedFirst Posted
Study publicly available on registry
March 17, 2022
CompletedStudy Start
First participant enrolled
September 30, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2029
August 1, 2025
July 1, 2025
5 years
February 22, 2022
July 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of patients for whom sMRI-guided therapy is technically successful
The percentage of participants for whom sMRI-guided therapy is successful will be reported as the percentage of participants who show no significant residual tumor after protocol therapy.
About 60 days
Incidence of Grade 3 irreversible or any Grade 4/5 neurologic toxicity.
The incidence of irreversible Grade 3 or any Grade 4/5 neurologic adverse events (AEs) or serious adverse events (SAEs) in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. Incidence of these toxicities will be reported for both cohorts, Cohort A (sMRI-Guided RT at 35 Gy in 10 fractions) and Cohort B (sMRI-Guided RT at 40 Gy in 10 fractions).
Up to 6 months
Secondary Outcomes (6)
Progression-Free Survival (PFS)
Up to 2 years
Overall Survival (OS)
Up to 2 years
Comparison of Cerebral Blood Volumes (CBV) among MRI techniques
About 3 months
Comparison of Apparent Diffusion Coefficients (ADC) among MRI techniques
About 3 months
Volume of enhancing disease at first progression compared to MRI volumes.
About 3 months
- +1 more secondary outcomes
Study Arms (2)
Cohort A: sMRI-Guided RT at 35 Gy in 10 fractions
EXPERIMENTALParticipants will receive a total dose of 3500 centigrays (cGY) (35Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 350 cGy (3.5 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique. Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT).
Cohort B: sMRI-Guided RT at 40 Gy in 10 fractions
EXPERIMENTALParticipants will receive a total dose of 4000 cGY (40Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 400 cGy (4 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique. Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT).
Interventions
Participants will receive radiation therapy delivered via intensity modulated proton therapy (IMPT) simultaneous integrated boost technique over a period of 10 days, 5 days per week for approximately 2 weeks.
Bevacizumab will be administered intravenously (IV), beginning at a dose of 10 mg/kg every 2-3 weeks until disease progression.
Eligibility Criteria
You may qualify if:
- A. Recurrent glioblastoma (or variants such as gliosarcoma) based on one of the following criteria:
- An area of MRI enhancement consistent with glioblastoma outside of the initial high dose radiation field.
- Biopsy or resection proven recurrent glioblastoma.
- Progressive glioblastoma based on advanced imaging (brain positron emission tomography (PET), perfusion MRI, or clinical MR Spectroscopy)
- B. Pathology diagnosis of glioblastoma, or variants such as gliosarcoma, on initial and/or reresection by 2021 WHO glioblastoma criteria. Prior pathology reports or specimens can be reexamined and reclassified as glioblastoma based on current criteria.
- C. Total area of recurrence on T1 post-contrast MRI (including all nodules of likely tumor) have a linear maximum measurement of 6 cm or less.
- D. Patients must have received prior brain radiation therapy for glioma in conventional fractionation (1.8 - 2 Gy per fraction, total dose maximum 63 Gy).
- E. Patients must have completed prior brain radiation four to six months or more prior to study treatment for recurrent tumors that are at least half based within the high dose (\> 46 Gy) radiation field.
- For "marginal" or "out of field" radiation failures where at least half of the enhancing disease is outside of the prior high dose radiation field but there is field overlap, patients must have completed prior radiation at least four months or more prior to study treatment.
- For "in field" radiation failures where at least half of the enhancing disease is within the prior high dose radiation field, patients must have completed prior radiation at least six months or more prior to study treatment.
- F. A minimum time must be elapsed from the administration of any prior anti-tumor or investigational agents to initiation of study treatments on this protocol as follows:
- days or 5 half-lives, whichever is shorter, elapsed from the administration of any experimental agent prior to initiation of study treatment.
- days elapsed from the administration of any prior cytotoxic agents except
- i. 14 days from vincristine and ≥ 21 days from procarbazine and Temozolomide (TMZ) prior to initiation of study treatment.
- G. Age at least 18.
- +16 more criteria
You may not qualify if:
- A. Brain malignancies other than glioblastoma (or variants such as gliosarcoma) by WHO 2021 criteria (benign lesions like meningioma are allowed)
- B. Glioma that has not previously undergone standard first line therapies including a first course of radiation therapy.
- C. Glioma that has already undergone a second course of radiation therapy.
- D. Multi-focal disease (separate enhancing nodules across multiple brain lobes). Note: Multiple nodules in the same region are allowed as long as the total linear diameter is 6 cm or less.
- E. Patients who have had treatment with Bevacizumab in the past.
- F. Patients who will receive chemotherapy concurrent with study therapy other than bevacizumab.
- G. Patients with recurrent Glioblastoma (rGBM) based in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: temporal lobe below the level of the floor of the third ventricle, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum (these regions have known sMRI artifact).
- H. Pregnant or breastfeeding patients.
- I. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year. Non-invasive tumors are permissible (e.g., carcinoma in situ).
- J. Severe active co-morbidities as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration.
- Transmural myocardial infarction within the last 6 months prior to registration.
- History of stroke or transient ischemic attack within 6 months prior to registration.
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Miami
Miami, Florida, 33136, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jonathan Bell, MD, PhD
University of Miami
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor of Clinical
Study Record Dates
First Submitted
February 22, 2022
First Posted
March 17, 2022
Study Start
September 30, 2022
Primary Completion (Estimated)
September 30, 2027
Study Completion (Estimated)
September 30, 2029
Last Updated
August 1, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share