Recurrent Glioblastoma
Conditions
Keywords
Recurrent glioblastoma, Radiation Therapy
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.
Interventions
RADIATIONMathematical 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.
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seizures | 6 months | Count of number of patients developing new/worsening seizures within 6 months of receiving protocol radiation therapy |
| Overall Survival (OS) | range of follow-up from date of registration was 1.2 - 38.6 months | 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. |
| Grade 3-5 Treatment-related Toxicity Rate | 6 Months | 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. |
| Number of Participants With Radiation Necrosis | 6 months | 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. |
| Median Local Recurrence-free Survival | 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. | 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. |
| Number of Participants Undergoing Salvage Craniotomy | 6 Months | Count of patients undergoing salvage craniotomy for resection or decompression of progressively enlarging tumor within 6 months of receipt of protocol radiation therapy. |
| Number of Participants Receiving Additional Systemic Treatments After Reirradiation | 6 Months | Count of patients undergoing systemic therapies for presumed recurrence or progression of disease within 6 months after receipt of protocol radiation therapy |
| Median Progression-Free Survival (PFS) | 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. | 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. |
Countries
United States
Participant flow
Pre-assignment details
There are no details to report.
Participants by arm
| Arm | Count |
|---|---|
| Mathematical Model-Adapted Radiation Mathematical Model-Adapted Radiation Fractionation Schedule
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. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Mathematical Model-Adapted Radiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 14 |
| other Total, other adverse events | 8 / 14 |
| serious Total, serious adverse events | 8 / 14 |
Outcome results
Primary
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.
Time frame: 10 Days
Population: All 14 participants were analyzed for the primary endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled | 14 Participants |
Secondary
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.
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Grade 3-5 Treatment-related Toxicity Rate | 0.29 proportion of treated participants |
Secondary
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Median Local Recurrence-free Survival | 6.2 Months |
Secondary
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Median Progression-Free Survival (PFS) | 4.3 Months |
Secondary
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
Time frame: 6 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Number of Participants Receiving Additional Systemic Treatments After Reirradiation | 3 Participants |
Secondary
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.
Time frame: 6 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Number of Participants Undergoing Salvage Craniotomy | 0 Participants |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Number of Participants With Radiation Necrosis | 0 Participants |
Secondary
Number of Participants With Seizures
Count of number of patients developing new/worsening seizures within 6 months of receiving protocol radiation therapy
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Number of Participants With Seizures | 1 Participants |
Secondary
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.
Time frame: range of follow-up from date of registration was 1.2 - 38.6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mathematical Model-Adapted Radiation | Overall Survival (OS) | 7.3 Months |