Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00108069
Status:
COMPLETED
Last Update Posted:
2015-11-05
First Post:
2005-04-12
Brief Title:
Tamoxifen and Bortezomib to Treat Recurrent Brain Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Trial of Tamoxifen and Bortezomib in Patients With Recurrent High-Grade Gliomas
Status:
COMPLETED
Status Verified Date:
2015-10
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:
This study will determine whether the drugs tamoxifen and bortezomib can delay tumor growth in patients with recurrent glioma malignant brain tumor Tamoxifen may work by interfering with the internal signaling needed for the cancer to grow Bortezomib may also interfere with tumor growth processes Laboratory studies show that low doses of bortezomib significantly enhance glioma cell death when used with tamoxifen
Patients 18 years of age and older with glioma whose tumor does not respond to standard medical treatment and who are not taking enzyme-inducing anti-seizure medications such as Dilantin phenobarbitol or Tegretol may be eligible for this study Candidates are screened with a physical examination blood tests and magnetic resonance imaging MRI or computed tomography CT MRI and CT scans produce images of the brain that can show if the brain tumor is growing see below
Participants receive treatment in 6-week cycles for up to 1 year The treatment duration may be extended in some patients who continue to tolerate the drug and show no signs of tumor growth after 1 year During each cycle patients take six tamoxifen tablets twice a day every day and receive bortezomib by infusion into a vein on days 3 6 10 13 24 27 31 and 34 Treatment may continue as long as the tumor does not grow and the patient does not develop unacceptable side effects In addition to drug treatment patients undergo the following tests and procedures
Periodic routine blood tests
MRI or CT scan of the head before starting each new cycle MRI uses a magnetic field and radio waves to produce images of body tissues and organs CT uses x-rays to provide 3-dimensional views of the part of the body being studied For both procedures the patient lies on a table that slides into the cylindrical scanner
Blood test to measure levels of bortezomib Blood is drawn before the bortezomib infusion on days 3 and 24 and 4 hours after the infusion on day 24 of the first treatment cycle only
Dynamic MRI with spectroscopy or positron emission tomography PET Patients may be asked to undergo one of these tests which help distinguish live tumor from dying tumor The experience of dynamic MRI with spectroscopy is the same as standard MRI and is done at the same time as the standard procedure see above PET uses a radioactive substance to show cellular activity in specific tissues of the body The patient is given an injection of a sugar solution in which a radioactive isotope has been attached to the sugar molecule A special camera detects the radiation emitted by the radioisotope and the resulting images show how much glucose is being used in various parts of the body Because rapidly growing cells such as tumors take up and use more glucose than normal cells do this test can be used to show active tumors
Drug diary Patients maintain a calendar to record when they take their study drugs and what side effects they develop
Patients 18 years of age and older with glioma whose tumor does not respond to standard medical treatment and who are not taking enzyme-inducing anti-seizure medications such as Dilantin phenobarbitol or Tegretol may be eligible for this study Candidates are screened with a physical examination blood tests and magnetic resonance imaging MRI or computed tomography CT MRI and CT scans produce images of the brain that can show if the brain tumor is growing see below
Participants receive treatment in 6-week cycles for up to 1 year The treatment duration may be extended in some patients who continue to tolerate the drug and show no signs of tumor growth after 1 year During each cycle patients take six tamoxifen tablets twice a day every day and receive bortezomib by infusion into a vein on days 3 6 10 13 24 27 31 and 34 Treatment may continue as long as the tumor does not grow and the patient does not develop unacceptable side effects In addition to drug treatment patients undergo the following tests and procedures
Periodic routine blood tests
MRI or CT scan of the head before starting each new cycle MRI uses a magnetic field and radio waves to produce images of body tissues and organs CT uses x-rays to provide 3-dimensional views of the part of the body being studied For both procedures the patient lies on a table that slides into the cylindrical scanner
Blood test to measure levels of bortezomib Blood is drawn before the bortezomib infusion on days 3 and 24 and 4 hours after the infusion on day 24 of the first treatment cycle only
Dynamic MRI with spectroscopy or positron emission tomography PET Patients may be asked to undergo one of these tests which help distinguish live tumor from dying tumor The experience of dynamic MRI with spectroscopy is the same as standard MRI and is done at the same time as the standard procedure see above PET uses a radioactive substance to show cellular activity in specific tissues of the body The patient is given an injection of a sugar solution in which a radioactive isotope has been attached to the sugar molecule A special camera detects the radiation emitted by the radioisotope and the resulting images show how much glucose is being used in various parts of the body Because rapidly growing cells such as tumors take up and use more glucose than normal cells do this test can be used to show active tumors
Drug diary Patients maintain a calendar to record when they take their study drugs and what side effects they develop
Detailed Description:
Background
Tamoxifen TAM a member of the selective estrogen receptor modulator SERM family is widely used in the treatment of estrogen receptor ER expressing breast cancer It has previously been shown that high-dose TAM has cytotoxic activity against glioma cells but whether this effect is drug-specific or represents a general property of SERMs was unknown We have now demonstrated that suppression of nuclear factor kappa-light-chain-enhancer of activated B cells NF-kB activation markedly enhances SERM-induced apoptosis suggesting a role for NF-kB in protecting glioma cells from SERM-induced cytotoxicity
Bortezomib is a potent inhibitor of the 26S proteosome and causes significant anti-proliferative and cytotoxic effects in a number of cell lines through its protean effects on a variety of cellular signaling pathways including its ability to potently inhibit the NF-kB pathway We have recently demonstrated that bortezomib has significant anti-glioma activity in vitro and a ongoing clinical trial has demonstrated some possible activity in patients with recurrent gliomas We have now also generated preclinical data demonstrating that bortezomib in combination with Tamoxifen has synergistic cytotoxic effects on glioma cells
Thus given the minimal to modest activity of both drugs in patients with recurrent gliomas given their spectrum of non-overlapping toxicities and given the marked synergistic glioma cell killing of the combination of drugs in our preclinical screens we are now proposing a phase II trial of bortezomib in combination with Tamoxifen in patients with recurrent gliomas not taking enzyme inducing anti-epileptic drugs EIAEDs
Objectives
The primary statistical endpoint will be response defined as either stable disease or objective response as is standard in neuro-oncology clinical trials after 6 weeks of treatment
Eligibility
Patients with histologically proven high-grade gliomas or patients with a clinical and radiographic diagnosis of brainstem glioma will be eligible for this protocol
Design
The phase II study will be stratified by the type of high grade glioma anaplastic glioma AA or glioblastoma GBM and a two-stage min-max design with a maximum of 41 patients in the GBM stratum and 36 patients in the AA stratum
Tamoxifen TAM a member of the selective estrogen receptor modulator SERM family is widely used in the treatment of estrogen receptor ER expressing breast cancer It has previously been shown that high-dose TAM has cytotoxic activity against glioma cells but whether this effect is drug-specific or represents a general property of SERMs was unknown We have now demonstrated that suppression of nuclear factor kappa-light-chain-enhancer of activated B cells NF-kB activation markedly enhances SERM-induced apoptosis suggesting a role for NF-kB in protecting glioma cells from SERM-induced cytotoxicity
Bortezomib is a potent inhibitor of the 26S proteosome and causes significant anti-proliferative and cytotoxic effects in a number of cell lines through its protean effects on a variety of cellular signaling pathways including its ability to potently inhibit the NF-kB pathway We have recently demonstrated that bortezomib has significant anti-glioma activity in vitro and a ongoing clinical trial has demonstrated some possible activity in patients with recurrent gliomas We have now also generated preclinical data demonstrating that bortezomib in combination with Tamoxifen has synergistic cytotoxic effects on glioma cells
Thus given the minimal to modest activity of both drugs in patients with recurrent gliomas given their spectrum of non-overlapping toxicities and given the marked synergistic glioma cell killing of the combination of drugs in our preclinical screens we are now proposing a phase II trial of bortezomib in combination with Tamoxifen in patients with recurrent gliomas not taking enzyme inducing anti-epileptic drugs EIAEDs
Objectives
The primary statistical endpoint will be response defined as either stable disease or objective response as is standard in neuro-oncology clinical trials after 6 weeks of treatment
Eligibility
Patients with histologically proven high-grade gliomas or patients with a clinical and radiographic diagnosis of brainstem glioma will be eligible for this protocol
Design
The phase II study will be stratified by the type of high grade glioma anaplastic glioma AA or glioblastoma GBM and a two-stage min-max design with a maximum of 41 patients in the GBM stratum and 36 patients in the AA stratum
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 |
|---|---|---|---|
| 05-C-0137 | None | None | None |