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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00042009 | Other Identifier | JHM IRB |
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The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
Radiation therapy (RT) is an integral component of the management of brain tumors, but cognitive deficits following cranial irradiation are well documented. There is an association between damage to neural progenitor cells (NPC) and neurocognitive dysfunction. NPC are similarly known to play an important role in recovery from damage to the brain, including radiation-induced damage. However NPC are extremely sensitive to radiation. In spite of this information, current RT planning techniques do not limit the radiation dose to the NPC containing regions. Recent human studies have demonstrated that it is possible to use intensity modulated radiation therapy to reduce the radiation dose to NPC containing regions during RT for brain tumors, without compromising coverage of the tumor. We hypothesize that NPC-sparing RT will reduce neurocognitive decline following treatment for brain tumors, without compromising tumor local control. However, there is conflicting data regarding the role of NPC in the development of glioblastoma multiforme (GBM). Some studies suggest that GBM are derived from NPC whereas others have associated NPC with improved tumor control following therapy for GBM. Prior to evaluation of neurocognitive outcomes with NPC-sparing RT, it is therefore imperative to evaluate whether NPC-sparing RT techniques lead to increased LR in the spared NPC containing niches of the brain.
The proposed study is designed to evaluate LR in the spared regions of the brain following NPC sparing RT in patients with newly diagnosed GBM. Our research will consist of 3 specific aims: 1) Determine the LR rate at 1 year in the spared NPC containing niches in patients treated with NPC sparing RT for GBM; 2) Quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with GBM; 3) Determine if it is feasible to evaluate cognitive function prospectively in patients undergoing NPC sparing RT for GBM.
The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neural Progenitor Cell Sparing Radiation with Temozolomide | Experimental | All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiation | Radiation | Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Local Recurrence in the Spared NPC Niches | Number of participants with local recurrence (LR) at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM). Local recurrence in spared area is defined as development of a new regions of T1 post gadolinium enhancement. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Extent of NPC Sparing | The extent of NPC-sparing will be recorded for each patient. Patients will be binned into 4 groups according to the volume of NPC region that receives a certain dose as follows: 1) V5Gy≤50%; 2) V5Gy ≤20%; 3) V10Gy≤20%; 4) Doses higher than levels 1-3. | 1 year |
| Distance of Tumor to Spared NPC Niches |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kristin Redmond, M.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States |
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3 participants were screen failures
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| ID | Title | Description |
|---|---|---|
| FG000 | Neural Progeniter Cell Sparing Radiation With Temozolomide | All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy Radiation: Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI. Chemotherapy: Temozolomide |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Neural Progeniter Cell Sparing Radiation With Temozolomide | All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy Radiation: Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI. Chemotherapy: Temozolomide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Number of Participants With Local Recurrence in the Spared NPC Niches | Number of participants with local recurrence (LR) at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM). Local recurrence in spared area is defined as development of a new regions of T1 post gadolinium enhancement. | Posted | Count of Participants | Participants | 1 year |
|
Up to 6 years (median follow-up time was 15.8 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Neural Progeniter Cell Sparing Radiation With Temozolomide | All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy Radiation: Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI. Chemotherapy: Temozolomide |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospital admission for anticoagulation of venous thrombosis due to disease progression | Nervous system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kristin Redmond, MD | Johns Hopkins University School of Medicine | 410-955-6980 | kjanson3@jhmi.edu |
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| 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 | Apr 1, 2014 | May 23, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D011827 | Radiation |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D055585 | Physical Phenomena |
| D013812 | Therapeutics |
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|
| Chemotherapy | Drug | Temozolomide |
|
The X-, Y-, and Z- coordinate distances in centimeters will be recorded from the most proximal point of the planning tumor volume to the closest point of the spared NPC-containing niche. |
| 1 year |
| Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest | Change in mean score of neurocognitive function (processing speed) as measured by WAIS-IV (Coding subtest) in patients treated with NPC sparing radiation for newly diagnosed GBM. The coding subtest of WAIS-IV is a visual, paper and pencil task that requires individuals to match numbers with symbols based on a "key" at the top of the page (Coding) by drawing the correct symbol in the boxes provided. Coding measures visual processing speed, short-term visual memory, and the ability to shift the eyes efficiently back and forth between the "key" and the responses. This task requires fine motor skills (using a pencil) but does not require expressive language. Minimal demands are placed on receptive language. This task also assesses the ability to sustain focus and effort for a two minutes. The score is the total number of correct responses within a given time frame, which ranges from 0-135. A higher score reflects a better outcome. A negative value for change reflects a worse outcome. | Change from baseline to 6 months |
| Change in Neurocognitive Function as Measured by Trail Making Test | Change in mean score of neurocognitive function as measured by Trail Making test Parts A and B in patients treated with NPC sparing radiation for newly diagnosed GBM. The Trail making score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. Score ranges from 0-150 for Part A and 0-300 for Part B. A higher score reflects greater neurocognitive impairment. Therefore, a negative value for change reflects an improvement in this measure, whereas a positive value reflects worsening impairment. | Change from baseline to 6 months |
| Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT) | Change in neurocognitive function (verbal fluency) as measured by COWAT in patients treated with NPC sparing radiation for newly diagnosed GBM. COWAT assesses verbal fluency by asking the participant to produce words for three designated letters. The test score is the total number of different words produced for all three letters. A higher score reflects a better outcome. Therefore, a positive value for change reflects an improvement in this measure. | Change from baseline to 6 months |
| Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) | Change in total recall, delayed recall, and recognition discrimination index as measured by HVLT-R in patients treated with NPC sparing radiation for newly diagnosed GBM. 12-item word list, composed of four words from each of the three semantic categories which the patient must learn over three trials. For each trial, the subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The score for total recall is the sum of all the correctly-recalled words from each trial, for a maximum of 36. Delayed recall is assessed as the number of words freely recalled 20-25 minutes after the learning trials. Recognition is assessed after 20-25 minutes where the patient is read 24 words and is asked to say "yes" after words from the recall list (12 targets) and "no" after other words (12 distractors). RDI is the number of recalled target words minus the number of recalled distractor words. A higher score reflects a better outcome. | Change from baseline to 6 months |
| Radiation Dose to Spared NPC Region | The mean radiation dose (cGy) to spared NPC region (hippocampus, subventricular zone [SVZ]) in reference to site of lesion. | Day 1 of radiation therapy |
| Volume (cc) of "NPC for Sparing" Region | The volume of the "NPC_for_sparing" region as collected using the Pinnacle treatment planning system. | day 1 of radiation therapy |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Education | Number of years of education | Median | Full Range | years |
|
| Education | Number of participants with greater than 12 years of education | Count of Participants | Participants |
|
| Mini-Mental State Exam (MMSE) | The MMSE is a questionnaire used to measure cognitive impairment. The score ranges from 0-30 with a higher score, reflecting less impairment. Degree of impairment is interpreted by the following scores: 25-30= Questionably significant, 20-25= mild, 10-20= moderate, 0-10= severe. | Median | Full Range | score on a scale |
|
| Multifocal Tumor | Count of Participants | Participants |
|
| MGMT promoter methylation | Count of Participants | Participants |
|
| Resection extent | Count of Participants | Participants |
|
|
|
| Secondary | Extent of NPC Sparing | The extent of NPC-sparing will be recorded for each patient. Patients will be binned into 4 groups according to the volume of NPC region that receives a certain dose as follows: 1) V5Gy≤50%; 2) V5Gy ≤20%; 3) V10Gy≤20%; 4) Doses higher than levels 1-3. | Data was not collected for this outcome measure | Posted | 1 year |
|
|
| Secondary | Distance of Tumor to Spared NPC Niches | The X-, Y-, and Z- coordinate distances in centimeters will be recorded from the most proximal point of the planning tumor volume to the closest point of the spared NPC-containing niche. | Data was not collected for this outcome measure. | Posted | 1 year |
|
|
| Secondary | Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest | Change in mean score of neurocognitive function (processing speed) as measured by WAIS-IV (Coding subtest) in patients treated with NPC sparing radiation for newly diagnosed GBM. The coding subtest of WAIS-IV is a visual, paper and pencil task that requires individuals to match numbers with symbols based on a "key" at the top of the page (Coding) by drawing the correct symbol in the boxes provided. Coding measures visual processing speed, short-term visual memory, and the ability to shift the eyes efficiently back and forth between the "key" and the responses. This task requires fine motor skills (using a pencil) but does not require expressive language. Minimal demands are placed on receptive language. This task also assesses the ability to sustain focus and effort for a two minutes. The score is the total number of correct responses within a given time frame, which ranges from 0-135. A higher score reflects a better outcome. A negative value for change reflects a worse outcome. | Paired baseline and follow-up scores were only available in 14/30 participants. | Posted | Mean | 95% Confidence Interval | correct responses | Change from baseline to 6 months |
|
|
|
| Secondary | Change in Neurocognitive Function as Measured by Trail Making Test | Change in mean score of neurocognitive function as measured by Trail Making test Parts A and B in patients treated with NPC sparing radiation for newly diagnosed GBM. The Trail making score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. Score ranges from 0-150 for Part A and 0-300 for Part B. A higher score reflects greater neurocognitive impairment. Therefore, a negative value for change reflects an improvement in this measure, whereas a positive value reflects worsening impairment. | Paired baseline and follow-up scores were only available in 12/30 participants. | Posted | Mean | 95% Confidence Interval | seconds | Change from baseline to 6 months |
|
|
|
| Secondary | Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT) | Change in neurocognitive function (verbal fluency) as measured by COWAT in patients treated with NPC sparing radiation for newly diagnosed GBM. COWAT assesses verbal fluency by asking the participant to produce words for three designated letters. The test score is the total number of different words produced for all three letters. A higher score reflects a better outcome. Therefore, a positive value for change reflects an improvement in this measure. | Paired baseline and follow-up scores were only available in 14/30 participants. | Posted | Mean | 95% Confidence Interval | words | Change from baseline to 6 months |
|
|
|
| Secondary | Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) | Change in total recall, delayed recall, and recognition discrimination index as measured by HVLT-R in patients treated with NPC sparing radiation for newly diagnosed GBM. 12-item word list, composed of four words from each of the three semantic categories which the patient must learn over three trials. For each trial, the subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The score for total recall is the sum of all the correctly-recalled words from each trial, for a maximum of 36. Delayed recall is assessed as the number of words freely recalled 20-25 minutes after the learning trials. Recognition is assessed after 20-25 minutes where the patient is read 24 words and is asked to say "yes" after words from the recall list (12 targets) and "no" after other words (12 distractors). RDI is the number of recalled target words minus the number of recalled distractor words. A higher score reflects a better outcome. | Paired baseline and follow-up scores were only available in 14/30 participants. | Posted | Mean | 95% Confidence Interval | words | Change from baseline to 6 months |
|
|
|
| Secondary | Radiation Dose to Spared NPC Region | The mean radiation dose (cGy) to spared NPC region (hippocampus, subventricular zone [SVZ]) in reference to site of lesion. | Posted | Mean | Full Range | centigray (cGy) | Day 1 of radiation therapy |
|
|
|
| Secondary | Volume (cc) of "NPC for Sparing" Region | The volume of the "NPC_for_sparing" region as collected using the Pinnacle treatment planning system. | Data was not collected for this outcome measure | Posted | day 1 of radiation therapy |
|
|
| 27 |
| 30 |
| 17 |
| 30 |
| 30 |
| 30 |
| Hospital admission for craniotomy for removal of tumor from disease progression. | Nervous system disorders | Non-systematic Assessment |
|
| Death due to disease progression. | Nervous system disorders | Non-systematic Assessment |
|
| Hospital admission for pneumonia. | Infections and infestations | Non-systematic Assessment |
|
| ER treatment for multifocal hemmorrhage due to head injury from fall. | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Hospital admission for progressive confusion. Treated for pneumatosis. | Infections and infestations | Non-systematic Assessment |
|
| Patient report of melanoma. Subsequently diagnosed mild/moderate melanocytic dysplasia. | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| ER due to seizure ending in car accident | Nervous system disorders | Non-systematic Assessment |
|
| Admission to surgery of tumor within treatment field for glioblastoma. | Nervous system disorders | Non-systematic Assessment |
|
| ER due to disorientation thought to be minor seizure. | Nervous system disorders | Non-systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| aphasia | Nervous system disorders | Systematic Assessment |
|
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| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| Title | Measurements |
|---|---|
|
|
| SVZ (Ipsilateral) |
|
| SVZ (Contralateral) |
|
| SVZ (Bilateral) |
|