Brain Cancer
Conditions
Keywords
Brain cancer, Glioblastoma, Glioblastoma Multiforme, GBM, Intensity Modulated Proton Radiotherapy, IMPT, Intensity Modulated Radiotherapy, IMRT, Radiotherapy, XRT, Cognitive tests, Thinking skills tests, Questionnaires, Surveys, Quality of life, QOL
Brief summary
The goal of this clinical research study is to compare IMRT with IMPT in patients with glioblastoma. Researchers want to learn about cognitive side effects (mental status changes) that may occur, such as memory loss and impaired thinking. IMRT is the delivery of focused radiation therapy using photon beams and advanced computer planning to help shape the dose in order to give the highest possible dose to the tumor with the least dose to surrounding normal tissues. IMPT is also focused radiation therapy similar to IMRT, but it uses proton particles to deliver the radiation instead of photon beams. IMPT also uses advanced computer planning in order to shape the dose to the target with the least dose to surrounding normal tissues.
Detailed description
Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group. If you are in Group 1, you will receive IMRT. If you are in Group 2, you will receive IMPT. Radiation Therapy: In both groups, you will receive radiation treatments each day, Monday-Friday, starting on Day 1. You will continue to receive radiation treatment until you have completed 30 total treatments. This is a total of up to 6 weeks of treatment. You will sign a separate consent form for the IMRT or IMPT that will explain the procedures and risks in detail. Study Visits: Before beginning radiation, you will have what is called a simulation to plan your radiation. During the simulation, you will be flat on your back on a computed tomography (CT) table and a soft plastic mask will be made to help hold your head still during treatment. This is the position you will be in when you receive radiation treatment. You will then have a CT scan, which will make computerized images to help plan your treatment. At Month 2 (+/- 30 days): * You will have a physical exam, including measurement of your vital signs. * You will have an MRI to check the status of the disease. * You will be asked about any drugs you may be taking and side effects you may be having. * You will complete the thinking skills tests and the questionnaires about your quality of life and symptoms. Length of Treatment: You may receive up to 6 weeks of radiation therapy. You will no longer be able to receive radiation therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your active participation on the study will be over after the follow-up visits. Follow-Up: At Month 4 (+/- 30 days) and then every 2 months for up to 2 years after radiation therapy: * You will have a physical exam, including measurement of your vital signs. * You will be asked about any side effects you may be having. * You will have an MRI to check the status of the disease. * You will complete the thinking skills tests and the questionnaires about your quality of life and symptoms. Starting 2 years after radiation therapy, the study staff will continue checking your medical record to find out about your health status from then on. This is an investigational study. IMRT is delivered using FDA-approved and commercially available methods. IMPT is investigational. Up to 90 participants will be enrolled in this study. All will be enrolled at MD Anderson.
Interventions
RADIATIONIMPT
IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.
RADIATIONIMRT
IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.
BEHAVIORALCognitive Tests
Cognitive tests given at baseline, 4 months, then every 2 months for 2 years.
BEHAVIORALQuestionnaires
Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological diagnosis of: Glioblastoma or Gliosarcoma (WHO Grade IV) adapted RPA class III, IV, or V. 2. All patients must be \>/=18 years of age. 3. All patients must sign informed consent verifying that they are aware of the investigational nature of this study in keeping with the rules and policies of MD Anderson Cancer Center. The only acceptable consent form is the one approved by MD Anderson IRB. 4. All patients must have a baseline Mini Mental Status Examination score \>/=21. 5. All patients must have a KPS \>/=70. 6. All patients must be eligible to have either IMRT or IMPT as determined by the study radiation oncologist. 7. All patients must be able to undergo MRI with and without contrast with a glomerular filtration rate (eGFR) greater than or equal to 30 mg/min/1.72 m2. 8. All patients must have adequate liver, renal, and hematologic function within 14 days of registration as defined by Aspartate Amino Transferase (AST)/Alanine Amino Transferase (ALT)/Alkaline Phosphatase \< 3 times normal, creatinine \</=1.7 mg/dl, BUN \</= 35mg/dl, absolute neutrophil count \>/=1,800 cells/mm3, Hemoglobin \>/= 10 g/dl, and platelet count \> 100,000. 9. All patients must be able to adequately read, write and speak to participate in the cognitive and quality of life assessments. However mild to moderate deficits in these functions due to tumor are allowed.
Exclusion criteria
1. Patients will be excluded if they are not planning to receive concurrent temozolomide. 2. Patients will be excluded if they have had prior radiation to the brain. 3. Patients will be excluded if they have had prior surgical resection of brain for other brain tumors. 4. Patients will be excluded if they are pregnant as assessed by serum beta human chorionic gonadotropin (b-HCG). A serum b-HCG test will be performed no greater than 14 days prior to study registration for women of childbearing potential. 5. Patients with gliomatosis will be excluded. 6. Patients with Gliadel bis-chloroethylnitrosourea (BCNU) implanted wafers will be excluded. 7. Patients weighing greater than 136 kilograms will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cognitive Failure | baseline, 4 months, then every 2 months for 2 years | Time to cognitive failure on any of 6 primary variables from pre-specified cognitive tests (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, TMT Part A or Part B, COWA) with failure defined as a decline that meets or exceeds the reliable change index (RCI) for each cognitive test variable. A cumulative incidence approach used to estimate median time to cognitive failure in order to account for the competing risks of disease progression and death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. |
| Progression Free Survival (PFS) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Participants last known to be alive and progression-free are censored at date of last contact. |
| Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | 2 years | The adverse severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0). Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated. Count of participants experiencing adverse events. Should a participant experience multiple adverse events at different grades, the patient is counted only once at the highest grade. |
Countries
United States
Participant flow
Recruitment details
Recruitment Details: May 2013- March 2016. All participants recruited at UT MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Intensity Modulated Proton Radiotherapy (IMPT) IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.
IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.
Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years.
Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years. | 28 |
| Intensity Modulated Radiotherapy (IMRT) IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.
IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.
Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years.
Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years. | 39 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Decided to get treatment locally | 1 | 5 |
| Overall Study | Denial of Insurance Coverage | 12 | 0 |
| Overall Study | Did Not Meet Eligibility Criteria | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Progression | 0 | 1 |
| Overall Study | Received IMR only due to insurance analysis | 1 | 0 |
Baseline characteristics
| Characteristic | Intensity Modulated Proton Radiotherapy (IMPT) | Intensity Modulated Radiotherapy (IMRT) | Total |
|---|---|---|---|
| Age, Continuous | 53 years | 55 years | 53.8 years |
| Race/Ethnicity, Customized African American | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 31 Participants | 57 Participants |
| Region of Enrollment United States | 28 participants | 39 participants | 67 participants |
| Sex: Female, Male Female | 12 Participants | 19 Participants | 31 Participants |
| Sex: Female, Male Male | 16 Participants | 20 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 41 | 22 / 26 |
| other Total, other adverse events | 29 / 41 | 19 / 26 |
| serious Total, serious adverse events | 2 / 41 | 1 / 26 |
Outcome results
Primary
Time to Cognitive Failure
Time to cognitive failure on any of 6 primary variables from pre-specified cognitive tests (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, TMT Part A or Part B, COWA) with failure defined as a decline that meets or exceeds the reliable change index (RCI) for each cognitive test variable. A cumulative incidence approach used to estimate median time to cognitive failure in order to account for the competing risks of disease progression and death.
Time frame: baseline, 4 months, then every 2 months for 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intensity Modulated Radiotherapy (IMRT) | Time to Cognitive Failure | 7.7 months |
| Intensity Modulated Proton Radiotherapy (IMPT) | Time to Cognitive Failure | 4.9 months |
p-value: 0.74Gray's test
Secondary
Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher)
The adverse severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0). Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated. Count of participants experiencing adverse events. Should a participant experience multiple adverse events at different grades, the patient is counted only once at the highest grade.
Time frame: 2 years
Population: Between June 2013 and March 2016, 90 patients consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intensity Modulated Radiotherapy (IMRT) | Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | Grade 4 Adverse Events | 2 Participants |
| Intensity Modulated Radiotherapy (IMRT) | Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | Grade 3 Adverse Events | 4 Participants |
| Intensity Modulated Radiotherapy (IMRT) | Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | Grade 2 Adverse Events | 14 Participants |
| Intensity Modulated Proton Radiotherapy (IMPT) | Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | Grade 4 Adverse Events | 1 Participants |
| Intensity Modulated Proton Radiotherapy (IMPT) | Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | Grade 3 Adverse Events | 2 Participants |
| Intensity Modulated Proton Radiotherapy (IMPT) | Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher) | Grade 2 Adverse Events | 5 Participants |
Secondary
Overall Survival
Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Population: Between June 2013 and March 2016, 90 participants consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intensity Modulated Radiotherapy (IMRT) | Overall Survival | 21.2 months |
| Intensity Modulated Proton Radiotherapy (IMPT) | Overall Survival | 24.5 months |
p-value: 0.6Log Rank
Secondary
Progression Free Survival (PFS)
Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Participants last known to be alive and progression-free are censored at date of last contact.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Population: Between June 2013 and March 2016, 90 patients consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intensity Modulated Radiotherapy (IMRT) | Progression Free Survival (PFS) | 8.9 months |
| Intensity Modulated Proton Radiotherapy (IMPT) | Progression Free Survival (PFS) | 6.6 months |
p-value: 0.24Log Rank