Ignite Creation Date:
2024-05-06 @ 1:29 AM
Last Modification Date:
2024-10-26 @ 11:05 AM
Study NCT ID:
NCT01822275
Status:
TERMINATED
Last Update Posted:
2022-12-29
First Post:
2013-03-22
Brief Title:
Phase II Trial of Low-Dose Whole Brain Radiotherapy With Concurrent Temozolomide and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma Multiforme
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Phase II Trial of Low-Dose Whole Brain Radiotherapy With Concurrent Temozolomide and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma Multiforme
Status:
TERMINATED
Status Verified Date:
2022-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Poor accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GCC 1224
Brief Summary:
In the current proposed trial the role of the low-dose WBRT 015 Gy would be to safely treat the microscopic distant GBM cells outside of the high dose RT region and sensitize the gross tumor while the focal radiation dose 185 Gy to the gross tumor will bring the total tumor dose of 2 Gy per fraction which is the standard of care
Radiotherapy RT has been integral in the treatment of GBM since the 1970s when Walker et al showed that post-operative whole brain radiotherapy WBRT offered significant improvements in median survival time and even more so when given with concomitant BCNU chemotherapy Ensuing dose escalation studies found the optimal dose to be 60 Gy Patients could not tolerate escalation to higher doses than 60 Gy with WBRT due to unacceptable toxicity Even with WBRT of 60 Gy a huge volume of healthy brain tissue was unnecessarily treated with high-dose radiation recurrences with WBRT remained overwhelmingly local Hochberg and Pruitt 1980 found that after WBRT only 3 of recurrences were outside 2 cm of the margins of the primary tumor With the rise of the CT scan in the 1980s and the MRI in the 1990s along with subsequent improvements in three-dimensional conformal radiation partial brain RT PBRT became practical since tumor margins could be visualized and irradiated more accurately - Subsequently WBRT was shown to provide no survival benefit over PBRT at the same dosage - thus the latter took over as the standard of care
Radiotherapy RT has been integral in the treatment of GBM since the 1970s when Walker et al showed that post-operative whole brain radiotherapy WBRT offered significant improvements in median survival time and even more so when given with concomitant BCNU chemotherapy Ensuing dose escalation studies found the optimal dose to be 60 Gy Patients could not tolerate escalation to higher doses than 60 Gy with WBRT due to unacceptable toxicity Even with WBRT of 60 Gy a huge volume of healthy brain tissue was unnecessarily treated with high-dose radiation recurrences with WBRT remained overwhelmingly local Hochberg and Pruitt 1980 found that after WBRT only 3 of recurrences were outside 2 cm of the margins of the primary tumor With the rise of the CT scan in the 1980s and the MRI in the 1990s along with subsequent improvements in three-dimensional conformal radiation partial brain RT PBRT became practical since tumor margins could be visualized and irradiated more accurately - Subsequently WBRT was shown to provide no survival benefit over PBRT at the same dosage - thus the latter took over as the standard of care
Detailed Description:
Radiation Therapy RT has been integral in the treatment of GBM since the 1970s Studies showed that post-operative whole brain radiotherapy WBRT offered significant improvements in median survival time and even more so when given with chemotherapy Even with WBRT a huge volume of healthy brain tissue was unnecessarily treated with high-dose radiation re-growth of tumor with WBRT remained overwhelmingly close to the original tumor site With the advances in imaging techniques like CT scans and MRIs partial brain RT PBRT has become a common practice PBRT is RT given only to the tumor or area of the brain where the cancer was removed PBRT given with a drug called temozolomide TMZ is used as the standard of care treatment for newly diagnosed GBM after surgery
Current data from our institution suggests that the combination of TMZ with very low-dose WBRT efficiently kills GBM cells WBRT at conventional higher doses is not given at the same time as TMZ since the severe toxicity risk would be too risky However a lower daily WBRT dose than what is conventionally given to patients should be tolerable The randomized trials studying TMZ with low-dose WBRT in patients with brain metastasis did not demonstrate increased serious toxicities associated with TMZ
PURPOSE OF STUDY Why is the research study being done The purpose of this study is to determine if low-dose WBRT given in combination with the standard of care TMZ regimen is safe and effective The role of the low-dose WBRT would be to safely treat the microscopic distant GBM cells outside of the high-dose PBRT region We will continue to target the tumor with focused PBRT that will bring the total tumor dose to the standard of care dose This study will find out what effects good or bad low-dose WBRT has on you and your cancer
PROCEDURES How many people will take part in the study About 47 people will take part in this study Patient participation in this study is voluntary The research will be conducted at UMMS
What will happen if I take part in this research study Before you begin the study Patient will need to have the following exams tests or procedures to find out if you can be in the study These exams tests or procedures are part of regular cancer care and may be done even if Patient does not join the study If heshe has had some of them recently they may not need to be repeated This will be up to the study doctor
History and physical with neurological examination
Brain MRI with contrast
Blood tests about 2-3 teaspoons of blood will be taken from the vein
Pregnancy test for women of childbearing potential
During the study The experimental part of this study is that the patient will receive low-dose WBRT If the tests show that the patient can be in the study and heshe chooses to take part patient will receive low-dose WBRT at the same time as standard PBRT The patient will receive RT once daily 5 days a week Monday through Friday for 6 weeks a total of 30 treatments Each treatment lasts for no more than 30 minutes Treatment will begin 3-6 weeks after your last surgery
At the same time as RT you will take oral TMZ once a day TMZ will be taken continuously from the night before the first day of RT to the last day of RT maximum of 49 days The pills should be swallowed whole and taken on an empty stomach therefore a minimum of 2 hours after eating and with no food consumption for at least 1 hour after TMZ administration The drug will be taken at night
About 4 weeks after you finish RT and TMZ you will begin 28 day cycles of TMZ alone You will take TMZ orally on the first 5 days of each cycle Again the pills should swallowed whole and taken on an empty stomach therefore a minimum of 2 hours after eating and with no food consumption for at least 1 hour after TMZ administration You should take the TMZ at night
If patient misses any dose of TMZ it will not be made up the next day
The patient will be treated with post-radiation TMZ for 6 cycles unless there is evidence of tumor progression or treatment-related toxicity Patients demonstrating continued benefit from the adjuvant treatment can continue treatment to a maximum of 12 cycles at the discretion of the treating physician
If the exams tests and procedures show that the patient can be in the study and they choose to take part then heshe will need the following tests and procedures They are part of regular cancer care
Weekly during RT and TMZ
Patient evaluation with toxicity assessment
Blood tests about 2-3 teaspoons of blood will be taken from the vein
Prior to starting each cycle of TMZ alone
History and physical with neurological examination and toxicity assessment
Blood tests about 2-3 teaspoons of blood will be taken from the vein
Prior to cycle 1 and then every 2-3 months a brain MRI with contrast
Blood tests about 2-3 teaspoons of blood will be taken from your vein will also be performed at about 2 and 3 weeks days 14 and 21 2days after starting cycle 1 and cycle 2 of TMZ alone
During follow-up
Once patient has completed all the cycles of TMZ the patient will be seen every 1-3 months for the first two years years 1-2 3-6 months for the next 2 years years 3-4 and then annually starting at year 5 During these follow-up visits the patient will have the following tests and procedures performed
History and physical with neurological examination and toxicity assessment
Brain MRI with contrast
Any other test deemed medically necessary
The doctors would like to keep track of the medical condition for the rest of the patients life Keeping in touch with the patient and checking on their condition yearly helps the physicians to look at the long-term effects of the study
Current data from our institution suggests that the combination of TMZ with very low-dose WBRT efficiently kills GBM cells WBRT at conventional higher doses is not given at the same time as TMZ since the severe toxicity risk would be too risky However a lower daily WBRT dose than what is conventionally given to patients should be tolerable The randomized trials studying TMZ with low-dose WBRT in patients with brain metastasis did not demonstrate increased serious toxicities associated with TMZ
PURPOSE OF STUDY Why is the research study being done The purpose of this study is to determine if low-dose WBRT given in combination with the standard of care TMZ regimen is safe and effective The role of the low-dose WBRT would be to safely treat the microscopic distant GBM cells outside of the high-dose PBRT region We will continue to target the tumor with focused PBRT that will bring the total tumor dose to the standard of care dose This study will find out what effects good or bad low-dose WBRT has on you and your cancer
PROCEDURES How many people will take part in the study About 47 people will take part in this study Patient participation in this study is voluntary The research will be conducted at UMMS
What will happen if I take part in this research study Before you begin the study Patient will need to have the following exams tests or procedures to find out if you can be in the study These exams tests or procedures are part of regular cancer care and may be done even if Patient does not join the study If heshe has had some of them recently they may not need to be repeated This will be up to the study doctor
History and physical with neurological examination
Brain MRI with contrast
Blood tests about 2-3 teaspoons of blood will be taken from the vein
Pregnancy test for women of childbearing potential
During the study The experimental part of this study is that the patient will receive low-dose WBRT If the tests show that the patient can be in the study and heshe chooses to take part patient will receive low-dose WBRT at the same time as standard PBRT The patient will receive RT once daily 5 days a week Monday through Friday for 6 weeks a total of 30 treatments Each treatment lasts for no more than 30 minutes Treatment will begin 3-6 weeks after your last surgery
At the same time as RT you will take oral TMZ once a day TMZ will be taken continuously from the night before the first day of RT to the last day of RT maximum of 49 days The pills should be swallowed whole and taken on an empty stomach therefore a minimum of 2 hours after eating and with no food consumption for at least 1 hour after TMZ administration The drug will be taken at night
About 4 weeks after you finish RT and TMZ you will begin 28 day cycles of TMZ alone You will take TMZ orally on the first 5 days of each cycle Again the pills should swallowed whole and taken on an empty stomach therefore a minimum of 2 hours after eating and with no food consumption for at least 1 hour after TMZ administration You should take the TMZ at night
If patient misses any dose of TMZ it will not be made up the next day
The patient will be treated with post-radiation TMZ for 6 cycles unless there is evidence of tumor progression or treatment-related toxicity Patients demonstrating continued benefit from the adjuvant treatment can continue treatment to a maximum of 12 cycles at the discretion of the treating physician
If the exams tests and procedures show that the patient can be in the study and they choose to take part then heshe will need the following tests and procedures They are part of regular cancer care
Weekly during RT and TMZ
Patient evaluation with toxicity assessment
Blood tests about 2-3 teaspoons of blood will be taken from the vein
Prior to starting each cycle of TMZ alone
History and physical with neurological examination and toxicity assessment
Blood tests about 2-3 teaspoons of blood will be taken from the vein
Prior to cycle 1 and then every 2-3 months a brain MRI with contrast
Blood tests about 2-3 teaspoons of blood will be taken from your vein will also be performed at about 2 and 3 weeks days 14 and 21 2days after starting cycle 1 and cycle 2 of TMZ alone
During follow-up
Once patient has completed all the cycles of TMZ the patient will be seen every 1-3 months for the first two years years 1-2 3-6 months for the next 2 years years 3-4 and then annually starting at year 5 During these follow-up visits the patient will have the following tests and procedures performed
History and physical with neurological examination and toxicity assessment
Brain MRI with contrast
Any other test deemed medically necessary
The doctors would like to keep track of the medical condition for the rest of the patients life Keeping in touch with the patient and checking on their condition yearly helps the physicians to look at the long-term effects of the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None