Trial Outcomes & Findings for Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide (NCT NCT01478854)

NCT ID: NCT01478854

Last Updated: 2019-06-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 33 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2019-06-13

Participant Flow

3 participants were screen failures

Participant milestones

Measure	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
Overall Study STARTED	30
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Neural Progeniter Cell Sparing Radiation With Temozolomide n=30 Participants 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
Age, Continuous	58 years n=30 Participants
Sex: Female, Male Female	14 Participants n=30 Participants
Sex: Female, Male Male	16 Participants n=30 Participants
Region of Enrollment United States	30 Participants n=30 Participants
Education	20 Participants n=30 Participants
Mini-Mental State Exam (MMSE)	26 score on a scale n=30 Participants
Multifocal Tumor	6 Participants n=30 Participants
MGMT promoter methylation Positive	8 Participants n=30 Participants
MGMT promoter methylation Negative	14 Participants n=30 Participants
MGMT promoter methylation Unknown	8 Participants n=30 Participants
Resection extent Gross total resection	17 Participants n=30 Participants
Resection extent Subtotal resection	13 Participants n=30 Participants

PRIMARY outcome

Timeframe: 1 year

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.

Outcome measures

Measure

Neural Progeniter Cell Sparing Radiation With Temozolomide n=30 Participants 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

Number of Participants With Local Recurrence in the Spared NPC Niches

0 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Data was not collected for this outcome measure

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: Data was not collected for this outcome measure.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change from baseline to 6 months

Population: Paired baseline and follow-up scores were only available in 14/30 participants.

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.

Outcome measures

Measure

Neural Progeniter Cell Sparing Radiation With Temozolomide n=14 Participants 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

Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest

-6.9 correct responses Interval -12.9 to -0.8

SECONDARY outcome

Timeframe: Change from baseline to 6 months

Population: Paired baseline and follow-up scores were only available in 12/30 participants.

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.

Outcome measures

Measure	Neural Progeniter Cell Sparing Radiation With Temozolomide n=12 Participants 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
Change in Neurocognitive Function as Measured by Trail Making Test Trail Making Test Part A	20.6 seconds Interval -21.4 to 62.6
Change in Neurocognitive Function as Measured by Trail Making Test Trail Making Test Part B	-14.7 seconds Interval -59.8 to 30.5

SECONDARY outcome

Timeframe: Change from baseline to 6 months

Population: Paired baseline and follow-up scores were only available in 14/30 participants.

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.

Outcome measures

Measure

Neural Progeniter Cell Sparing Radiation With Temozolomide n=14 Participants 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

Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT)

2.6 words Interval -2.8 to 8.1

SECONDARY outcome

Timeframe: Change from baseline to 6 months

Population: Paired baseline and follow-up scores were only available in 14/30 participants.

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.

Outcome measures

Measure	Neural Progeniter Cell Sparing Radiation With Temozolomide n=14 Participants 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
Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) Total recall	-1.4 words Interval -4.1 to 1.3
Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed recall	-0.6 words Interval -2.4 to 1.1
Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) Recognition Discrimination Index (RDI)	-0.3 words Interval -1.4 to 0.8

SECONDARY outcome

Timeframe: Day 1 of radiation therapy

The mean radiation dose (cGy) to spared NPC region (hippocampus, subventricular zone [SVZ]) in reference to site of lesion.

Outcome measures

Measure	Neural Progeniter Cell Sparing Radiation With Temozolomide n=30 Participants 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
Radiation Dose to Spared NPC Region SVZ (Ipsilateral)	4181 centigray (cGy) Interval 605.0 to 5970.0
Radiation Dose to Spared NPC Region SVZ (Contralateral)	1986 centigray (cGy) Interval 440.0 to 5358.0
Radiation Dose to Spared NPC Region SVZ (Bilateral)	3096 centigray (cGy) Interval 601.0 to 5481.0
Radiation Dose to Spared NPC Region Hippocampus (Ipsilateral)	4906 centigray (cGy) Interval 90.0 to 6139.0
Radiation Dose to Spared NPC Region Hippocampus (Contralateral)	1652 centigray (cGy) Interval 87.0 to 3584.0
Radiation Dose to Spared NPC Region Hippocampus (Bilateral)	3473 centigray (cGy) Interval 88.0 to 4820.0

SECONDARY outcome

Timeframe: day 1 of radiation therapy

Population: Data was not collected for this outcome measure

The volume of the "NPC_for_sparing" region as collected using the Pinnacle treatment planning system.

Outcome measures

Outcome data not reported

Adverse Events

Neural Progeniter Cell Sparing Radiation With Temozolomide

Serious events: 17 serious events

Other events: 30 other events

Deaths: 27 deaths

Serious adverse events

Measure	Neural Progeniter Cell Sparing Radiation With Temozolomide n=30 participants at risk 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
Nervous system disorders Hospital admission for anticoagulation of venous thrombosis due to disease progression	13.3% 4/30 • Number of events 4 • Up to 6 years (median follow-up time was 15.8 months)
Nervous system disorders Hospital admission for craniotomy for removal of tumor from disease progression.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Nervous system disorders Death due to disease progression.	16.7% 5/30 • Number of events 5 • Up to 6 years (median follow-up time was 15.8 months)
Infections and infestations Hospital admission for pneumonia.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Injury, poisoning and procedural complications ER treatment for multifocal hemmorrhage due to head injury from fall.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Infections and infestations Hospital admission for progressive confusion. Treated for pneumatosis.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Skin and subcutaneous tissue disorders Patient report of melanoma. Subsequently diagnosed mild/moderate melanocytic dysplasia.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Nervous system disorders ER due to seizure ending in car accident	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Nervous system disorders Admission to surgery of tumor within treatment field for glioblastoma.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)
Nervous system disorders ER due to disorientation thought to be minor seizure.	3.3% 1/30 • Number of events 1 • Up to 6 years (median follow-up time was 15.8 months)

Other adverse events

Measure	Neural Progeniter Cell Sparing Radiation With Temozolomide n=30 participants at risk 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
General disorders Fatigue	66.7% 20/30 • Up to 6 years (median follow-up time was 15.8 months)
Gastrointestinal disorders diarrhea	43.3% 13/30 • Up to 6 years (median follow-up time was 15.8 months)
Nervous system disorders aphasia	23.3% 7/30 • Up to 6 years (median follow-up time was 15.8 months)

Additional Information

Kristin Redmond, MD

Johns Hopkins University School of Medicine

Phone: 410-955-6980

Email: kjanson3@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place