Ignite Creation Date:
2024-05-05 @ 11:21 PM
Last Modification Date:
2024-10-26 @ 10:33 AM
Study NCT ID:
NCT01316809
Status:
COMPLETED
Last Update Posted:
2019-12-12
First Post:
2011-03-15
Brief Title:
AZD8055 for Adults With Recurrent Gliomas
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Trial of AZD8055 An Oral MTOR Kinase Inhibitor for Adults With Recurrent Gliomas
Status:
COMPLETED
Status Verified Date:
2016-04-14
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
- AZD8055 is an experimental cancer treatment drug that works by inhibiting a protein called mTOR which is known to promote tumor cell and blood vessel growth and to control tumor s energy and nutrient levels AZD8055 is the first drug that inhibits both types of mTOR protein and is expected to be more effective than prior mTOR inhibitors However more research is needed to determine its safety and effectiveness in treating brain tumors known as gliomas that have not responded to standard treatments
Objectives
- To evaluate the safety and effectiveness of AZD8055 in individuals with gliomas that have not responded to standard treatments
Eligibility
- Individuals at least 18 years of age who have been diagnosed with gliomas that have not responded to standard chemotherapy surgery or radiation
Design
Participants will be screened with a physical examination medical history blood tests and tumor imaging studies
Participants will be separated into two treatment groups one group that will receive surgery to remove the glioma and one that will not have surgical treatment
Participants in the nonsurgical treatment group will take AZD8055 by mouth daily for a 42-day cycle of treatment Participants will keep a diary to record doses and keep track of any side effects
Participants in the surgical treatment group will take AZD8055 by mouth daily for 7 days and then will have tumor removal surgery At least 3 weeks after surgery participants will resume doses of AZD8055 and will continue to take the drug for as long as the tumor does not recur
During treatment participants will have regular visits to the clinical center involving frequent blood and urine tests and other examinations to monitor the effects of treatment Participants will have imaging studies to study the cancers response to the treatment
Participants will continue to have cycles of treatment for as long as the treatment continues to be effective and the side effects are not severe enough to stop participation in the study
- AZD8055 is an experimental cancer treatment drug that works by inhibiting a protein called mTOR which is known to promote tumor cell and blood vessel growth and to control tumor s energy and nutrient levels AZD8055 is the first drug that inhibits both types of mTOR protein and is expected to be more effective than prior mTOR inhibitors However more research is needed to determine its safety and effectiveness in treating brain tumors known as gliomas that have not responded to standard treatments
Objectives
- To evaluate the safety and effectiveness of AZD8055 in individuals with gliomas that have not responded to standard treatments
Eligibility
- Individuals at least 18 years of age who have been diagnosed with gliomas that have not responded to standard chemotherapy surgery or radiation
Design
Participants will be screened with a physical examination medical history blood tests and tumor imaging studies
Participants will be separated into two treatment groups one group that will receive surgery to remove the glioma and one that will not have surgical treatment
Participants in the nonsurgical treatment group will take AZD8055 by mouth daily for a 42-day cycle of treatment Participants will keep a diary to record doses and keep track of any side effects
Participants in the surgical treatment group will take AZD8055 by mouth daily for 7 days and then will have tumor removal surgery At least 3 weeks after surgery participants will resume doses of AZD8055 and will continue to take the drug for as long as the tumor does not recur
During treatment participants will have regular visits to the clinical center involving frequent blood and urine tests and other examinations to monitor the effects of treatment Participants will have imaging studies to study the cancers response to the treatment
Participants will continue to have cycles of treatment for as long as the treatment continues to be effective and the side effects are not severe enough to stop participation in the study
Detailed Description:
Background
Recurrent glioma patients have very limited treatment options A significant percentage of gliomas have increased activity of the PI3KAktmTOR pathway mostly due to loss of PTEN
AZD8055 is a first in-class inhibitor of the kinase activity of mTOR specifically inhibiting both mTORC1 and mTORC2 complexes Preclinical data generated in the Neuro-Oncology Branch Laboratory of Dr Howard Fine demonstrated that AZD8055 has significant anti-glioma activity in vivo and in vitro
Objectives
To establish the maximally tolerated dose MTD of continuous once daily AZD8055 in patients with recurrent malignant gliomas not on enzyme-inducing anti-epileptic drugs EIAED
To generate pharmacokinetic data on continuous once daily AZD8055 dosing
Eligibility
-Patients with histologically proven glioma are eligible for this study Patients should have failed prior standard treatment with radiotherapy
Design
This study will accrue up to 24 evaluable patients non-surgical arm Cohorts of 3 or 6 patients will receive continuous AZD8055 once daily orally for 42 days The MTD will be based on the tolerability observed during the first 6 weeks of treatment only Up to three patients may be enrolled simultaneously at each dose level The dose of AZD8055 can be progressively escalated if only 03 or 16 patients experience a dose limiting toxicity at the prior dose level
A subset of patients in whom tumor re-resection is considered standard of care will receive 1-week treatment with AZD8055 and then undergo resection Patients will be treated at the highest dose level shown to be safe at the time of enrollment Once patients recover from surgery they will restart treatment with AZD8055 and stay on treatment as long as there is no tumor progression or protocol-mandated removal criteria Management of toxicity will be the same as non-surgical patients receiving their second and subsequent cycles of therapy as delineated in the protocol Up to 12 patients will enter the surgical arm of this trial
The accrual ceiling will be open to 42 patients to factor in replacing those who come off
treatment prior to cycle 1
-At the end of Cycle 1 patients in both treatment arms surgical and non-surgical may choose to continue to receive AZD8055 until disease progression or until they experience unmanageable drug related toxicity as long as they are continuing to derive clinical benefit and do not fulfill any of the criteria for removal from protocol therapy
Recurrent glioma patients have very limited treatment options A significant percentage of gliomas have increased activity of the PI3KAktmTOR pathway mostly due to loss of PTEN
AZD8055 is a first in-class inhibitor of the kinase activity of mTOR specifically inhibiting both mTORC1 and mTORC2 complexes Preclinical data generated in the Neuro-Oncology Branch Laboratory of Dr Howard Fine demonstrated that AZD8055 has significant anti-glioma activity in vivo and in vitro
Objectives
To establish the maximally tolerated dose MTD of continuous once daily AZD8055 in patients with recurrent malignant gliomas not on enzyme-inducing anti-epileptic drugs EIAED
To generate pharmacokinetic data on continuous once daily AZD8055 dosing
Eligibility
-Patients with histologically proven glioma are eligible for this study Patients should have failed prior standard treatment with radiotherapy
Design
This study will accrue up to 24 evaluable patients non-surgical arm Cohorts of 3 or 6 patients will receive continuous AZD8055 once daily orally for 42 days The MTD will be based on the tolerability observed during the first 6 weeks of treatment only Up to three patients may be enrolled simultaneously at each dose level The dose of AZD8055 can be progressively escalated if only 03 or 16 patients experience a dose limiting toxicity at the prior dose level
A subset of patients in whom tumor re-resection is considered standard of care will receive 1-week treatment with AZD8055 and then undergo resection Patients will be treated at the highest dose level shown to be safe at the time of enrollment Once patients recover from surgery they will restart treatment with AZD8055 and stay on treatment as long as there is no tumor progression or protocol-mandated removal criteria Management of toxicity will be the same as non-surgical patients receiving their second and subsequent cycles of therapy as delineated in the protocol Up to 12 patients will enter the surgical arm of this trial
The accrual ceiling will be open to 42 patients to factor in replacing those who come off
treatment prior to cycle 1
-At the end of Cycle 1 patients in both treatment arms surgical and non-surgical may choose to continue to receive AZD8055 until disease progression or until they experience unmanageable drug related toxicity as long as they are continuing to derive clinical benefit and do not fulfill any of the criteria for removal from protocol therapy
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 11-C-0122 | None | None | None |