Ignite Creation Date:
2024-05-05 @ 6:32 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00493376
Status:
TERMINATED
Last Update Posted:
2012-02-02
First Post:
2007-06-26
Brief Title:
Study of Tumour Response to Tirapazamine During Treatment of Cervical Cancer
Sponsor:
British Columbia Cancer Agency
Organization:
British Columbia Cancer Agency
Study Overview
Official Title:
Prospective Study of Tirapazamine Targeting in Cervical Cancer
Status:
TERMINATED
Status Verified Date:
2012-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
This study was a companion study to another one The other study closed early so this one did as well
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is as follows
to determine whether tirapazamine damages cervical tumour DNA immediately after its administration
to determine the blood flow and oxygen level of cervical tumour before and after treatment with tirapazamine
to determine whether tirapazamine damages cervical tumour DNA immediately after its administration
to determine the blood flow and oxygen level of cervical tumour before and after treatment with tirapazamine
Detailed Description:
Patients with locally advanced cervical cancer can have a poor clinical outcome with standard cisplatin and pelvic radiation therapy It is well established that pre-treatment tumor hypoxia is a significant prognostic factor in tumors and may be one of the most important and modifiable mechanisms of radiation resistance in this group of tumours Significant levels of hypoxia are not present in all locally advanced cervical tumors Hence measurement of the pretreatment tumour oxygenation status is imperative and can be assessed using various means Immunohistochemical staining of various intrinsic hypoxia markers to include Ca9 Glut1 HIF-1 alpha on the pre-treatment tumours can be performed
Tirapazamine a bio-reductively activated hypoxic cell selective anti-tumour agent has been found to act synergistically with cisplatinum resulting in a significantly higher cell kill than expected based on additive action We proposed to measure the cell killing effect of tirapazamine with the following tests
Comet assay Tirapazamine causes DNA damage that can predict for cell killing by measuring DNA damage in cells from tumor biopsies using the alkaline comet assay
Measurement of phosphorylation of histone gamma H2AX It has been explored as a measure of radiosensitivity in response to clinically relevant doses of radiation The histone gamma H2AX phosphorylation can be used to detect tirapazamine induced DNA double-strand breaks and collapsed replication forks
There is some evidence that the drug delivery may be impaired and in fact the drug may not actually be reaching all of the hypoxic tumour cells A recent study has shown that in an experimental setting tirapazamine causes a decrease in vascular perfusion which can be measured with contrast enhanced MRI We propose to assess if this mechanism is operative in human tumours
Clinical studies have demonstrated that tumour vascular can increase during the course of radiation therapy consistent with re-oxygenation and that this is suggestive of a better outcome Tumours that become less hypoxic during the course of therapy have an increased likelihood of response to the given treatment However response to tirapazamine may be reduced In order to assess both the vascular change that may occur directly because of tirapazamine infusion as well as any increase in tumour vascularity and perhaps increase in tumour oxygenation during the course of therapy we plan to assess these tumours during the course of therapy Assessment of tumour perfusion and vessel permeability after 10 radiation treatments on day 12 of chemo-radiation therapy will be performed via T1 weighted dynamic contrast enhanced MRI DCMRI
We hypothesize that
1 Tirapazamine a hypoxic cell cytotoxin and radiosensitizer will result in increased DNA damage and a better clinical outcome if
1 the pre-treatment tumor demonstrates significant hypoxia
2 tirapazamine treatment results in increased DNA damage
2 tirapazamine acts in part by changing vascular perfusion in the tumour and that these changes can be measured with dynamic contrast enhanced MRI
Tirapazamine a bio-reductively activated hypoxic cell selective anti-tumour agent has been found to act synergistically with cisplatinum resulting in a significantly higher cell kill than expected based on additive action We proposed to measure the cell killing effect of tirapazamine with the following tests
Comet assay Tirapazamine causes DNA damage that can predict for cell killing by measuring DNA damage in cells from tumor biopsies using the alkaline comet assay
Measurement of phosphorylation of histone gamma H2AX It has been explored as a measure of radiosensitivity in response to clinically relevant doses of radiation The histone gamma H2AX phosphorylation can be used to detect tirapazamine induced DNA double-strand breaks and collapsed replication forks
There is some evidence that the drug delivery may be impaired and in fact the drug may not actually be reaching all of the hypoxic tumour cells A recent study has shown that in an experimental setting tirapazamine causes a decrease in vascular perfusion which can be measured with contrast enhanced MRI We propose to assess if this mechanism is operative in human tumours
Clinical studies have demonstrated that tumour vascular can increase during the course of radiation therapy consistent with re-oxygenation and that this is suggestive of a better outcome Tumours that become less hypoxic during the course of therapy have an increased likelihood of response to the given treatment However response to tirapazamine may be reduced In order to assess both the vascular change that may occur directly because of tirapazamine infusion as well as any increase in tumour vascularity and perhaps increase in tumour oxygenation during the course of therapy we plan to assess these tumours during the course of therapy Assessment of tumour perfusion and vessel permeability after 10 radiation treatments on day 12 of chemo-radiation therapy will be performed via T1 weighted dynamic contrast enhanced MRI DCMRI
We hypothesize that
1 Tirapazamine a hypoxic cell cytotoxin and radiosensitizer will result in increased DNA damage and a better clinical outcome if
1 the pre-treatment tumor demonstrates significant hypoxia
2 tirapazamine treatment results in increased DNA damage
2 tirapazamine acts in part by changing vascular perfusion in the tumour and that these changes can be measured with dynamic contrast enhanced MRI
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