Recurrent Glioma
Conditions
Keywords
glioma
Brief summary
The primary objective of step 1 is the rate of adverse events of minocycline and bevacizumab during reirradiation and of step 2 is the response rate to bevacizumab, reirradiation, and minocycline. The secondary objectives are the response rate, Progression Free Survival (PFS)-3, PFS-6, and effects on quality of life and cognition from repeat radiation and bevacizumab.
Detailed description
After providing informed consent, patients will undergo screening for eligibility to participate in the study. Screening will start within 21 days prior to dosing. Subjects will have an MRI within 21 days of starting radiation. QOL and cognition measures will be performed within 21 days of starting radiation. Radiation will be given with parameters determined on an individual basis by the radiation oncologist. Bevacizumab will be continued at 10mg/kg IV every 2 weeks. Minocycline will be given twice a day starting at 100mg PO bid. MRI, QOL, and cognitive tests will be obtained 1, 3 and 6 months after the end of radiation.
Interventions
DRUGBevacizumab
Bevacizumab will be administered in accordance with the FDA-approved dose for gliomas, 10mg/kg IV every 2 weeks. Bevacizumab will be continued every two weeks as long as tolerated. One cycle of bevacizumab will be 28 days, with treatments on day1 and day 15.
DRUGMinocycline
Minocycline will be given by mouth twice a day at the assigned dose level. Minocycline will be started on the day prior to radiation and continued until progression or intolerance.
RADIATIONRadiation
Radiation planning will be individualized by the radiation oncologist based on the location of the current radiation field relative to prior radiation doses. The length and fractionation will be determined individually by the radiation oncologist.
Sponsors
University of Utah
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ≥18 years old with a life expectancy of at least 8 weeks 2. Radiographically proven recurrent (≥ first relapse), intracranial glioma 3. Previous treatment with external beam radiation 4. Radiographic progression on current or prior bevacizumab treatment 5. Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug, and for 3 months after the last dose. 6. Karnofsky performance status of ≥50 7. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb \>9 g/dL, platelet count ≥50 x 109/L, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5x ULN, creatinine ≤1.5x ULN) 8. Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements 9. Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to study registration 10. Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study registration 11. Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight (LMW) heparin) must have no active bleeding or pathological condition that carries a high risk of bleeding, and must be on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
Exclusion criteria
1. Use of an investigational drug within 14 days or within 5 half-lives of teh investigational drug, whichever is shorter 2. Progression within 3 months of previous radiation by Radiographic Assessment in Neurooncology (RANO) criteria 3. History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage 4. A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy). 5. Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results 6. Women of child-bearing potential who are pregnant or breast feeding 7. Unstable angina and/or congestive heart failure in the last 6 months, transmural myocardial infarction within the last 6 months, New York Heart Association grade II or higher congestive heart failure requiring hospitalization within 12 months prior to registration, evidence of recent myocardial infarction by EKG performed within 14 days of registration, serious or inadequately controlled cardiac arrhythmia, significant vascular and peripheral vascular disease, evidence of bleeding diathesis or coagulopathy 8. History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months 9. Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection 10. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration 11. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose of study treatment to 28 days following radiation therapy (7-8 weeks) | Adverse Events were assessed from start of minocycline treatment (one day prior to start of radiation therapy) until 28 days following the end of radiation therapy. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. Events were categorized as severe (grade 3-4) or non-severe (grade 1-2). All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any non-severe AE and the number of patients who experienced any severe AE. A full listing of AEs (severe and non-severe) are listed in the Adverse Events module of the Results section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) at 6 Months | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | Proportion of patients who have not progressed 26 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. Estimates were done by Kaplan-Meier methods to account for patients whose data was censored prior to progression. |
| Tabulation of Tumor Best Responses | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | Tabulation of the best tumor response participants achieved from baseline through 26 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. |
| Quality of Life Change Over Time | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | The M. D. Anderson Symptom Inventory - Brain Tumors (MDASI-BT) scale was used to assess patients at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Means and standard deviations from baseline and 26 post-radiation are reported here. MDASI-BT is a 28 item assessment using a 0-10 scale. Part 1 contains 22 items and assesses severity of symptoms, with a score range from 0 to 220. Part 2 contains 6 items and assesses the degree to which symptoms interfere with daily life, with a score range from 0 to 60. The Total score adds Part 1 and Part 2 together to assess total symptom burden, with a score range from 0 to 280. For all parts of the assessment, higher scores indicate a lower quality of life and worse symptom burden. |
| Progression Free Survival (PFS) at 3 Months | From start of study treatment until 12 weeks after radiation therapy (15-16 weeks) | Proportion of patients who have not progressed 12 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. Estimates were done by Kaplan-Meier methods to account for patients whose data was censored prior to progression. |
| Cognitive Change Over Time - IDN | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Identification Test (IDN) measures basic information processing and decision speed. IDN is scored based on the speed of performance: mean of the log10 transformed reaction time for correct responses \[measured in log10 milliseconds (MS)\]. Lower scores meant a better performance. |
| Cognitive Change Over Time - OCLT | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. One Card Learning Test (OCLT) measures visuoperceptual learning and memory. OCLT is a score defined as the arcsine transformation of the square root of the proportion of correct responses to 80 OCLT questions. The transformed score ranges from 0 to 1.5708 where a higher score means better performance. |
| Cognitive Change Over Time - GMLT | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Groton Maze Learning Test (GMLT) measures special learning and executive functioning, including working memory, error monitoring, and ability to integrate feedback to modify problem solving. GMLT score is the number of errors made (lower score indicates better performance). |
| Cognitive Change Over Time - DET | From start of study treatment until 26 weeks after radiation therapy (29-30 weeks) | The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Detection Test (DET) measures sensory registration, vigilance, and reaction time. DET is scored based on the speed of performance: mean of the log10 transformed reaction time for correct responses \[measured in log10 milliseconds (MS)\]. Lower scores meant a better performance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 0: 100 mg Bid Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy. | 6 |
| Dose Level 1: 200 mg Bid Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy. | 3 |
| Dose Level 2: 400 mg Bid Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy. | 13 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Level 0: 100 mg Bid | Dose Level 1: 200 mg Bid | Dose Level 2: 400 mg Bid | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 2 Participants | 11 Participants | 18 Participants |
| Age, Continuous | 55.33 years STANDARD_DEVIATION 14.45 | 55 years | 53 years | 55.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 12 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 13 Participants | 20 Participants |
| Sex/Gender, Customized Female | 3 Participants | 0 Participants | 4 Participants | 7 Participants |
| Sex/Gender, Customized Male | 2 Participants | 3 Participants | 9 Participants | 14 Participants |
| Sex/Gender, Customized Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 6 | 0 / 3 | 2 / 13 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 11 / 13 |
| serious Total, serious adverse events | 1 / 6 | 0 / 3 | 8 / 13 |
Outcome results
Primary
Number of Participants With Adverse Events
Adverse Events were assessed from start of minocycline treatment (one day prior to start of radiation therapy) until 28 days following the end of radiation therapy. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. Events were categorized as severe (grade 3-4) or non-severe (grade 1-2). All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any non-severe AE and the number of patients who experienced any severe AE. A full listing of AEs (severe and non-severe) are listed in the Adverse Events module of the Results section.
Time frame: From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)
Population: In dose level 0, three patients were withdrawn prior to completing the reporting period for the primary objective, making them unevaluable, and they were replaced.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 0: 100 mg Bid | Number of Participants With Adverse Events | Any Severe (G3-4) Adverse Event | 0 Participants |
| Dose Level 0: 100 mg Bid | Number of Participants With Adverse Events | Any Non-Severe (G1-2) Adverse Event | 3 Participants |
| Dose Level 1: 200 mg Bid | Number of Participants With Adverse Events | Any Severe (G3-4) Adverse Event | 1 Participants |
| Dose Level 1: 200 mg Bid | Number of Participants With Adverse Events | Any Non-Severe (G1-2) Adverse Event | 3 Participants |
| Dose Level 2: 400 mg Bid | Number of Participants With Adverse Events | Any Severe (G3-4) Adverse Event | 3 Participants |
| Dose Level 2: 400 mg Bid | Number of Participants With Adverse Events | Any Non-Severe (G1-2) Adverse Event | 11 Participants |
Secondary
Cognitive Change Over Time - DET
The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Detection Test (DET) measures sensory registration, vigilance, and reaction time. DET is scored based on the speed of performance: mean of the log10 transformed reaction time for correct responses \[measured in log10 milliseconds (MS)\]. Lower scores meant a better performance.
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: 14 patients completed the baseline assessment and 3 patients completed the 26 weeks post radiation therapy assessment. Patients were not required to complete the Cogstate assessment if they took more than one hour to complete it, or if they could not operate a computer or if they could not complete the practice tests.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - DET | Baseline | 2.72 log10 ms | Standard Deviation 0.2 |
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - DET | 26 Weeks Post Radiation | 2.79 log10 ms | — |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - DET | Baseline | 2.51 log10 ms | Standard Deviation 0.1 |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - DET | 26 Weeks Post Radiation | 2.9 log10 ms | — |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - DET | Baseline | 2.62 log10 ms | Standard Deviation 0.11 |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - DET | 26 Weeks Post Radiation | 2.67 log10 ms | — |
Secondary
Cognitive Change Over Time - GMLT
The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Groton Maze Learning Test (GMLT) measures special learning and executive functioning, including working memory, error monitoring, and ability to integrate feedback to modify problem solving. GMLT score is the number of errors made (lower score indicates better performance).
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: 16 patients completed the baseline assessment and 3 patients completed the 26 weeks post radiation therapy assessment. Patients were not required to complete the Cogstate assessment if they took more than one hour to complete it, or if they could not operate a computer or if they could not complete the practice tests.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - GMLT | Baseline | 96.4 errors | Standard Deviation 31.17 |
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - GMLT | 26 Weeks Post Radiation | 61 errors | — |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - GMLT | Baseline | 90.67 errors | Standard Deviation 38.55 |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - GMLT | 26 Weeks Post Radiation | 87 errors | — |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - GMLT | Baseline | 84.38 errors | Standard Deviation 31.46 |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - GMLT | 26 Weeks Post Radiation | 48 errors | — |
Secondary
Cognitive Change Over Time - IDN
The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Identification Test (IDN) measures basic information processing and decision speed. IDN is scored based on the speed of performance: mean of the log10 transformed reaction time for correct responses \[measured in log10 milliseconds (MS)\]. Lower scores meant a better performance.
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: 16 patients completed the baseline assessment and 3 patients completed the 26 weeks post radiation therapy assessment. Patients were not required to complete the Cogstate assessment if they took more than one hour to complete it, or if they could not operate a computer or if they could not complete the practice tests.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - IDN | 26 Weeks Post Radiation | 2.89 log10 MS | — |
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - IDN | Baseline | 2.86 log10 MS | Standard Deviation 0.08 |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - IDN | Baseline | 2.72 log10 MS | Standard Deviation 0.05 |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - IDN | 26 Weeks Post Radiation | 2.97 log10 MS | — |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - IDN | Baseline | 2.78 log10 MS | Standard Deviation 0.07 |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - IDN | 26 Weeks Post Radiation | 2.78 log10 MS | — |
Secondary
Cognitive Change Over Time - OCLT
The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. One Card Learning Test (OCLT) measures visuoperceptual learning and memory. OCLT is a score defined as the arcsine transformation of the square root of the proportion of correct responses to 80 OCLT questions. The transformed score ranges from 0 to 1.5708 where a higher score means better performance.
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: 16 patients completed the baseline assessment and 3 patients completed the 26 weeks post radiation therapy assessment. Patients were not required to complete the Cogstate assessment if they took more than one hour to complete it, or if they could not operate a computer or if they could not complete the practice tests.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - OCLT | Baseline | 0.95 Arcsine [(sqrt) proportion correct] | Standard Deviation 0.18 |
| Dose Level 0: 100 mg Bid | Cognitive Change Over Time - OCLT | 26 Weeks Post Radiation | 0.94 Arcsine [(sqrt) proportion correct] | — |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - OCLT | Baseline | 0.91 Arcsine [(sqrt) proportion correct] | Standard Deviation 0.23 |
| Dose Level 1: 200 mg Bid | Cognitive Change Over Time - OCLT | 26 Weeks Post Radiation | 0.71 Arcsine [(sqrt) proportion correct] | — |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - OCLT | Baseline | 0.85 Arcsine [(sqrt) proportion correct] | Standard Deviation 0.15 |
| Dose Level 2: 400 mg Bid | Cognitive Change Over Time - OCLT | 26 Weeks Post Radiation | 0.96 Arcsine [(sqrt) proportion correct] | — |
Secondary
Progression Free Survival (PFS) at 3 Months
Proportion of patients who have not progressed 12 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. Estimates were done by Kaplan-Meier methods to account for patients whose data was censored prior to progression.
Time frame: From start of study treatment until 12 weeks after radiation therapy (15-16 weeks)
Population: Patients who did not complete the Dose Limiting Toxicity (DLT) evaluation period (3 patients in Dose Level 0) were excluded from PFS analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 0: 100 mg Bid | Progression Free Survival (PFS) at 3 Months | 1.000 probability of survival |
| Dose Level 1: 200 mg Bid | Progression Free Survival (PFS) at 3 Months | 0.667 probability of survival |
| Dose Level 2: 400 mg Bid | Progression Free Survival (PFS) at 3 Months | 0.646 probability of survival |
Secondary
Progression Free Survival (PFS) at 6 Months
Proportion of patients who have not progressed 26 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. Estimates were done by Kaplan-Meier methods to account for patients whose data was censored prior to progression.
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: Patients who did not complete the DLT period (3 patients in Dose Level 0) were excluded from PFS analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 0: 100 mg Bid | Progression Free Survival (PFS) at 6 Months | 0.667 probability of survival |
| Dose Level 1: 200 mg Bid | Progression Free Survival (PFS) at 6 Months | 0.333 probability of survival |
| Dose Level 2: 400 mg Bid | Progression Free Survival (PFS) at 6 Months | 0.277 probability of survival |
Secondary
Quality of Life Change Over Time
The M. D. Anderson Symptom Inventory - Brain Tumors (MDASI-BT) scale was used to assess patients at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Means and standard deviations from baseline and 26 post-radiation are reported here. MDASI-BT is a 28 item assessment using a 0-10 scale. Part 1 contains 22 items and assesses severity of symptoms, with a score range from 0 to 220. Part 2 contains 6 items and assesses the degree to which symptoms interfere with daily life, with a score range from 0 to 60. The Total score adds Part 1 and Part 2 together to assess total symptom burden, with a score range from 0 to 280. For all parts of the assessment, higher scores indicate a lower quality of life and worse symptom burden.
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: 22 patient completed the baseline questionnaire, and 4 patients completed the 26 week post-radiation questionnaire.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level 0: 100 mg Bid | Quality of Life Change Over Time | Baseline - Part 1 Score | 45.83 units on a scale | Standard Deviation 33.43 |
| Dose Level 0: 100 mg Bid | Quality of Life Change Over Time | Baseline - Total Score | 61.5 units on a scale | Standard Deviation 43.91 |
| Dose Level 0: 100 mg Bid | Quality of Life Change Over Time | Baseline - Part 2 Score | 15.67 units on a scale | Standard Deviation 12.61 |
| Dose Level 0: 100 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Part 1 Score | 48 units on a scale | Standard Deviation 0 |
| Dose Level 0: 100 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Part 2 Score | 22 units on a scale | Standard Deviation 12.73 |
| Dose Level 0: 100 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Total Score | 70 units on a scale | Standard Deviation 12.73 |
| Dose Level 1: 200 mg Bid | Quality of Life Change Over Time | Baseline - Part 2 Score | 11.67 units on a scale | Standard Deviation 7.51 |
| Dose Level 1: 200 mg Bid | Quality of Life Change Over Time | Baseline - Total Score | 41.33 units on a scale | Standard Deviation 24.09 |
| Dose Level 1: 200 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Part 1 Score | 55 units on a scale | — |
| Dose Level 1: 200 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Total Score | 84 units on a scale | — |
| Dose Level 1: 200 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Part 2 Score | 29 units on a scale | — |
| Dose Level 1: 200 mg Bid | Quality of Life Change Over Time | Baseline - Part 1 Score | 29.67 units on a scale | Standard Deviation 18.77 |
| Dose Level 2: 400 mg Bid | Quality of Life Change Over Time | Baseline - Part 1 Score | 39.08 units on a scale | Standard Deviation 24.23 |
| Dose Level 2: 400 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Part 2 Score | 15 units on a scale | — |
| Dose Level 2: 400 mg Bid | Quality of Life Change Over Time | Baseline - Total Score | 55.92 units on a scale | Standard Deviation 37.78 |
| Dose Level 2: 400 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Total Score | 29 units on a scale | — |
| Dose Level 2: 400 mg Bid | Quality of Life Change Over Time | Baseline - Part 2 Score | 16.85 units on a scale | Standard Deviation 15.38 |
| Dose Level 2: 400 mg Bid | Quality of Life Change Over Time | 26 Week Post Radiation - Part 1 Score | 14 units on a scale | — |
Secondary
Tabulation of Tumor Best Responses
Tabulation of the best tumor response participants achieved from baseline through 26 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response.
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Population: In Dose Level 0, three patients did not complete any follow-up scans and were excluded from analysis. In Dose Level 2, six patients did not complete any follow-up scans and were excluded from analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 0: 100 mg Bid | Tabulation of Tumor Best Responses | Partial Response | 0 Participants |
| Dose Level 0: 100 mg Bid | Tabulation of Tumor Best Responses | Complete Response | 1 Participants |
| Dose Level 0: 100 mg Bid | Tabulation of Tumor Best Responses | Stable Disease | 2 Participants |
| Dose Level 0: 100 mg Bid | Tabulation of Tumor Best Responses | Progressive Disease | 0 Participants |
| Dose Level 0: 100 mg Bid | Tabulation of Tumor Best Responses | Not Evaluable per RANO Criteria | 0 Participants |
| Dose Level 1: 200 mg Bid | Tabulation of Tumor Best Responses | Partial Response | 1 Participants |
| Dose Level 1: 200 mg Bid | Tabulation of Tumor Best Responses | Not Evaluable per RANO Criteria | 0 Participants |
| Dose Level 1: 200 mg Bid | Tabulation of Tumor Best Responses | Progressive Disease | 1 Participants |
| Dose Level 1: 200 mg Bid | Tabulation of Tumor Best Responses | Stable Disease | 1 Participants |
| Dose Level 1: 200 mg Bid | Tabulation of Tumor Best Responses | Complete Response | 0 Participants |
| Dose Level 2: 400 mg Bid | Tabulation of Tumor Best Responses | Stable Disease | 5 Participants |
| Dose Level 2: 400 mg Bid | Tabulation of Tumor Best Responses | Partial Response | 0 Participants |
| Dose Level 2: 400 mg Bid | Tabulation of Tumor Best Responses | Complete Response | 0 Participants |
| Dose Level 2: 400 mg Bid | Tabulation of Tumor Best Responses | Not Evaluable per RANO Criteria | 1 Participants |
| Dose Level 2: 400 mg Bid | Tabulation of Tumor Best Responses | Progressive Disease | 1 Participants |