Not provided
Not provided
Not provided
Not provided
trial stopped due to low accrual
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will evaluate the rate of radiation necrosis following treatment with immune checkpoint inhibitor (ICI) treatment and radiation therapy in subjects with metastatic brain cancer. Subjects will be treated with the standard of care immunotherapy followed by radiation therapy via stereotactic radiosurgery at a reduced dose.
This is a prospective, single arm, pilot study to determine the symptomatic radiation necrosis rate at 6 months utilizing dose-reduced stereotactic radiosurgery with immunotherapy for subjects with a diagnosis of 1-10 brain metastases from MRI and tissue diagnosis of primary malignancy.
Primary end-point is 6 month symptomatic radiation necrosis, defined as a 6-month rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. Follow-up MRIs will be fused with the planning scan for this assessment.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reduced Dose Stereotactic Radiosurgery | Experimental | Subjects will receive one stereotactic radiosurgery (SRS) treatment at a reduced dose based on the brain tumor size concurrently with their standard of care immunotherapy. Subjects will undergo follow up with clinical exams and brain MRI scans at 1, 3, 6, 9, and 12 months post SRS treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Reduced Dose SRS | Radiation | Subjects will receive SRS treatment at a reduced dose based on the brain tumor size |
|
| Measure | Description | Time Frame |
|---|---|---|
| Symptomatic Radiation Necrosis Proportion | The observed proportion of evaluable patients with symptomatic radiation necrosis by 6-months. Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Symptomatic Radiation Necrosis Rate | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kevin Shiue, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University Health Hospital | Indianapolis | Indiana | 46202 | United States | ||
| Indiana University Methodist Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32477016 | Derived | McClelland S 3rd, Lautenschlaeger T, Zang Y, Hanna NH, Shiue K, Kamer AP, Agrawal N, Ellsworth SG, Rhome RM, Watson GA. Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol. Rep Pract Oncol Radiother. 2020 Jul-Aug;25(4):500-506. doi: 10.1016/j.rpor.2020.04.007. Epub 2020 Apr 23. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Reduced Dose Stereotactic Radiosurgery With Immunotherapy | Subjects will receive one stereotactic radiosurgery (SRS) treatment at a reduced dose based on the brain tumor size concurrently with their standard of care immunotherapy. Subjects will undergo follow up with clinical exams and brain MRI scans at 1, 3, 6, 9, and 12 months post SRS treatment Reduced Dose SRS: Subjects will receive SRS treatment at a reduced dose based on the brain tumor size |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Includes the patients who started treatment and completed the required follow-up period for the study's primary outcome.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Reduced Dose Stereotactic Radiosurgery | Subjects will receive one stereotactic radiosurgery (SRS) treatment at a reduced dose based on the brain tumor size concurrently with their standard of care immunotherapy. Subjects will undergo follow up with clinical exams and brain MRI scans at 1, 3, 6, 9, and 12 months post SRS treatment Reduced Dose SRS: Subjects will receive SRS treatment at a reduced dose based on the brain tumor size |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Symptomatic Radiation Necrosis Proportion | The observed proportion of evaluable patients with symptomatic radiation necrosis by 6-months. Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. | Includes those patients who were evaluable for the 6-month outcomes. | Posted | Number | 95% Confidence Interval | proportion of participants | 6 months |
|
Up to 28 Months
Adverse events reported are those that are related to the SRS treatment and are as of February 2024. Patients are still on follow-up for the study and treatment-related adverse events can still occur. Patients were considered at risk for an adverse event if they started SRS treatment. For all-cause mortality and serious adverse events, treatment attribution was not considered.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Reduced Dose Stereotactic Radiosurgery With Immunotherapy | Subjects will receive one stereotactic radiosurgery (SRS) treatment at a reduced dose based on the brain tumor size concurrently with their standard of care immunotherapy. Subjects will undergo follow up with clinical exams and brain MRI scans at 1, 3, 6, 9, and 12 months post SRS treatment Reduced Dose SRS: Subjects will receive SRS treatment at a reduced dose based on the brain tumor size |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | CTCAE (5.0) | Non-systematic Assessment |
Early termination leading to small numbers of subjects analyzed
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kevin Shiue, MD | Indiana University Health | 317 944 2524 | kshiue@iuhealth.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 10, 2024 | Jun 28, 2024 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 6 months |
| Symptomatic Radiation Necrosis Rate | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Symptomatic Radiation Necrosis by SRS Group | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Symptomatic Radiation Necrosis by Brain Metastases Group | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Symptomatic Radiation Necrosis by Immune Checkpoint Inhibitor (ICI) Group | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Ppatients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Local Control | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | 6 months |
| Local Control | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Local Control by SRS Group | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Local Control by Brain Metastases Group | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Local Control by Immune Checkpoint Inhibitor (ICI) Group | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Radiographic Radiation Necrosis Rate | Radiographic radiation necrosis was defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of radiographic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | 6 months |
| Radiographic Radiation Necrosis Rate | Radiographic radiation necrosis was defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of radiographic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | 12 months |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| Oregon Health and Sciences | Portland | Oregon | 97239 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Corticosteroid Use at Baseline | Count of Participants | Participants |
|
| Diagnosis-Specific Graded Prognostic Assessment (ds-GPA) Median Survival at Baseline | ds-GPA values were calculated using brainmetgpa.com. Survival and the factors that predict survival vary by diagnosis and the molecular profile of the patient's tumor. | Median | Inter-Quartile Range | years |
|
| Primary Site of Initial Cancer Diagnosis | Count of Participants | Participants |
|
| Number of Lesions at Baseline | Median | Inter-Quartile Range | lesions |
|
|
|
|
| Secondary | Symptomatic Radiation Necrosis Rate | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 6-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 6 months |
|
|
|
| Secondary | Symptomatic Radiation Necrosis Rate | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
| Secondary | Symptomatic Radiation Necrosis by SRS Group | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
|
| Secondary | Symptomatic Radiation Necrosis by Brain Metastases Group | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
|
| Secondary | Symptomatic Radiation Necrosis by Immune Checkpoint Inhibitor (ICI) Group | Symptomatic radiation necrosis was defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Ppatients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
|
| Secondary | Local Control | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | Includes patients evaluable for 6-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 6 months |
|
|
|
| Secondary | Local Control | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | Includes patients evaluable for 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
| Secondary | Local Control by SRS Group | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | Includes patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
|
| Secondary | Local Control by Brain Metastases Group | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | Includes patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
|
| Secondary | Local Control by Immune Checkpoint Inhibitor (ICI) Group | Local control was defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired. | Includes patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
|
| Secondary | Radiographic Radiation Necrosis Rate | Radiographic radiation necrosis was defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of radiographic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 6-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 6 months |
|
|
|
| Secondary | Radiographic Radiation Necrosis Rate | Radiographic radiation necrosis was defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of radiographic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired. | Includes the patients who were evaluable for the 12-month outcomes. | Posted | Number | 95% Confidence Interval | survival probability | 12 months |
|
|
|
| 1 |
| 18 |
| 1 |
| 18 |
| 7 |
| 18 |
| Headache | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |