Clinical trial NCT03557372: Mathematical Model-Adapted Radiation In Glioblastoma
Official title: Mathematical Model-Adapted Radiation Fractionation Schedule for Patients With Recurrent Glioblastoma (MARS-Glio)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Recurrent Glioblastoma
Keywords: Recurrent glioblastoma
Radiation Therapy
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2018-06-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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
* Exclusion Criteria
* 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.

Primary outcomes:
measure: Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled
timeFrame: 10 Days
Secondary outcomes:
measure: Number of Participants With Radiation Necrosis
timeFrame: 6 months
measure: Number of Participants With Seizures
timeFrame: 6 months
measure: Overall Survival (OS)
timeFrame: range of follow-up from date of registration was 1.2 - 38.6 months
measure: Grade 3-5 Treatment-related Toxicity Rate
timeFrame: 6 Months
measure: Median Progression-Free Survival (PFS)
timeFrame: 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.
measure: Median Local Recurrence-free Survival
timeFrame: 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.
measure: Number of Participants Undergoing Salvage Craniotomy
timeFrame: 6 Months
measure: Number of Participants Receiving Additional Systemic Treatments After Reirradiation
timeFrame: 6 Months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shyam Tanguturi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.