Glioblastoma MultiformeNCT01478854
Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide
A study testing Radiation and Chemotherapy in people with Glioblastoma Multiforme, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Radiation and Chemotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Dec 2011to 25 Apr 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have newly diagnosed Glioblastoma Multiforme (GBM).
- Patient must have undergone surgical resection and must begin radiation within 12 weeks of this procedure.
- Patients must not have received previous irradiation to the brain.
- Patient must be at least 18 years of age
- Karnofsky performance status of greater than 60%
- Patient must receive temozolomide concurrent with and following radiation.
Show all 9Show fewer
- If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception for the duration of study participation and for up to 12 weeks following the study. Should a women become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.
- Patient must have the ability to understand and the willingness to sign a written informed consent document.
- All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines.
Who cannot join
- Patients may not be receiving any other agents to treat their GBM
- No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 2 years.
- Patients with any other uncontrolled illness will be excluded.
- Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. This applies to any woman who has not experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Male subjects must also agree to use effective contraception for the same period as above.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
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.
Read the detailed description
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.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Radiation, Chemotherapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
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.
ChemotherapyDrug
Temozolomide
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Radiation: Radiation; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (8)
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.
Measured: 1 year
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: day 1 of radiation therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study start27 Dec 2011
- Primary completion25 Apr 2018
- Study completion25 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristin Redmond, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478854
- Sponsor's protocol ID
- J10100
- Other IDs
- NA_00042009
- Status last verified
- Jun 2019
- First submitted
- 3 Nov 2011
- Last updated
- 13 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT01478854
- Acronym / sponsor ID
- J10100
- Conditions
- Glioblastoma Multiforme
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- 27 Dec 2011 (actual)
- Primary completion
- 25 Apr 2018 (actual)
- Study completion
- 25 Apr 2018 (actual)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Posted 12 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neural Progenitor Cell Sparing Radiation with Temozolomide | Experimental | Radiation: Radiation, Drug: ChemotherapyAll subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient must have newly diagnosed Glioblastoma Multiforme (GBM).
- Patient must have undergone surgical resection and must begin radiation within 12 weeks of this procedure.
- Patients must not have received previous irradiation to the brain.
- Patient must be at least 18 years of age
- Karnofsky performance status of greater than 60%
Key exclusion criteria (4 listed)
- Patients may not be receiving any other agents to treat their GBM
- No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 2 years.
- Patients with any other uncontrolled illness will be excluded.
- Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. This applies to any woman who has not experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Male subjects must also agree to use effective contraception for the same period as above.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiationPatients 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. | Radiation | Neural Progenitor Cell Sparing Radiation with Temozolomide |
| ChemotherapyTemozolomide | Drug | Neural Progenitor Cell Sparing Radiation with Temozolomide |
Primary outcome
Number of Participants With Local Recurrence in the Spared NPC Niches
Time frame: 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.
8 secondary outcomes
Extent of NPC Sparing
Time frame: 1 year
Distance of Tumor to Spared NPC Niches
Time frame: 1 year
Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest
Time frame: Change from baseline to 6 months
Change in Neurocognitive Function as Measured by Trail Making Test
Time frame: Change from baseline to 6 months
Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT)
Time frame: 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)
Time frame: Change from baseline to 6 months
Radiation Dose to Spared NPC Region
Time frame: Day 1 of radiation therapy
Volume (cc) of "NPC for Sparing" Region
Time frame: day 1 of radiation therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristin Redmond, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiation and Chemotherapy in people with Glioblastoma Multiforme, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Local Recurrence in the Spared NPC Niches (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2019.