Ignite Creation Date:
2024-05-05 @ 5:14 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00410865
Status:
TERMINATED
Last Update Posted:
2011-12-07
First Post:
2006-12-11
Brief Title:
Wild Type p53 Adenovirus for Oral Premalignancies
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
Clinical Protocol for Wild Type p53 Gene Induction in Premalignancies of Squamous Epithelium of the Oral Cavity and Oral Pharynx Via an Adenoviral Vector NCI Supplied Agent Ad-p53 INGN 201 Advexin NSC 683550 IND 7135
Status:
TERMINATED
Status Verified Date:
2011-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Sponsor withdrawl prior to study completion
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary Objectives
1 To determine the maximum tolerated dose and transduction efficiency of adenoviral mediated wild type p53 gene transfer in premalignancies of the upper aerodigestive tract
2 To determine the efficacy of single agent adenoviral mediated wild type p53 gene transfer in reversing oral premalignancies
1 To determine the maximum tolerated dose and transduction efficiency of adenoviral mediated wild type p53 gene transfer in premalignancies of the upper aerodigestive tract
2 To determine the efficacy of single agent adenoviral mediated wild type p53 gene transfer in reversing oral premalignancies
Detailed Description:
Some cancers that occur in the mouth may in some way be due to a defect in a gene called the p53 gene In this study an adenovirus is used as a tool a vector to deliver the normal p53 gene into cells The parts of the adenovirus that allow it to reproduce and promote infection are removed and the experimental gene p53 is added
Prior to beginning this study all participants will have a complete medical history and physical exam including measurement of vital signs and weight Participants will have an electrocardiogram ECG a urine test and blood tests including an HIV test At mid-cycle another white blood cell count will have to be drawn Women able to have children must have a negative blood pregnancy test Participants will be asked what medications have been taken in the past 30 days Additionally a chest x-ray will be performed
All participants will undergo a complete head and neck examination This includes both visual direct as well as mirror and fiberoptic if required of all mucosal sites from the nasal and lip areas to the back of the throat The physician will manually examine areas of the skin salivary glands the neck and thyroid bed Also the doctor will make sure the cranial nerves are working properly Location and size of lesions will be recorded and measured in two dimensions All lesions present will be photographed prior to the start of the intervention
Physical examination including a fiberoptic exam is the established standard of evaluating pre-cancerous lesions Only if a concern for cancer is present or symptoms are beyond those findings of the physical examination will a CT or MRI be prescribed These tests CT and MRI should not have to be done since they have no established role in the evaluation management or follow-up of these lesions If utilized a CT computerized tomography scan is a special test using x-ray along with a computer to give detailed pictures of parts of the body An MRI magnetic resonance imaging is a special test using a strong magnetic field and radio frequency signals to give detailed pictures of parts of the body An x-ray shows a 2-dimensional picture while a CT scan or an MRI shows 3 dimensions
Each study course includes one week of treatment followed by three weeks of observation The length of the study is 6 months 6 courses for most participants Participants will return to the clinic twice a day for Days 2 - 5 for each month of participation and should expect to spend a total of about 6 hours a day at the clinic
Participants in this study will receive INGN 201 in two ways The first way will be by injection in the area of the lesion The second way will be by mouth rinse Vital signs will be checked each time before participants receive INGN 201 The injection will be given on the first day of each week of the course after a numbing anesthetic medication is applied to prevent discomfort
The mouth rinse will be given one time on the first day and two times on Days 2 - 5 of each course of INGN 201 The injection and rinse first day of each cycle or the two rinses Days 2 - 5 of each cycle will be separated by at least two hours There will be a 30 second rinse with 5 acetic acid a raspberry flavored vinegar-like liquid followed by a tap water rinse just before participants receive INGN 201 Participants will be asked to hold the INGN 201 in their mouth for 30 minutes Eating and drinking should be avoided for one hour after receiving the mouth rinse The injection and rinse series will be repeated on a monthly basis for a period of six months
Participants will be requested to have two biopsies small tissue samples of the premalignant lesion taken on Day 5 of the 1st and 6th courses These biopsies will contribute to the understanding of how the experimental agent works on pre-cancerous cells In particular the biopsies will help to determine if the experimental agent is effective in killing pre-cancerous cells this process is called apoptosis These studies will also determine if the gene therapy injections have been effective in delivering the gene p53 to the precancerous cells
Participants will be observed for three more weeks after the sixth course of treatment At the end of the study 28 days after the last dose of INGN 201 participants will have a physical exam including measurement of weight and vital signs Participants will have a medical history and blood and urine tests These tests are done to monitor the effects of the study treatment
Participants who develop severe side effects will be taken off study though they may continue to receive follow-up evaluations to monitor their health Participants will be counseled by their physician should the lesions progress to cancer during the study or follow up period After counseling participant may choose to have surgery to remove the precancerous lesions laser surgery or observation The participant will then be monitored closely
Study participants will be followed for five years and must agree to stay in contact with their personal doctor or the doctor responsible for this study even if they move after the study ends The participants personal doctor may be asked to provide information about any anticancer treatments received after the studys completion as well as information about the patients overall health
This is an investigational study This experimental use of human genes is an example of gene therapy This is the first time that adenovirus gene therapy has been used for a pre-cancerous condition This is the first study to use INGN 201 as a mouth rinse A total of 20 patients will be enrolled at M D Anderson A maximum of 51 subjects will be entered in this multi-center study
Prior to beginning this study all participants will have a complete medical history and physical exam including measurement of vital signs and weight Participants will have an electrocardiogram ECG a urine test and blood tests including an HIV test At mid-cycle another white blood cell count will have to be drawn Women able to have children must have a negative blood pregnancy test Participants will be asked what medications have been taken in the past 30 days Additionally a chest x-ray will be performed
All participants will undergo a complete head and neck examination This includes both visual direct as well as mirror and fiberoptic if required of all mucosal sites from the nasal and lip areas to the back of the throat The physician will manually examine areas of the skin salivary glands the neck and thyroid bed Also the doctor will make sure the cranial nerves are working properly Location and size of lesions will be recorded and measured in two dimensions All lesions present will be photographed prior to the start of the intervention
Physical examination including a fiberoptic exam is the established standard of evaluating pre-cancerous lesions Only if a concern for cancer is present or symptoms are beyond those findings of the physical examination will a CT or MRI be prescribed These tests CT and MRI should not have to be done since they have no established role in the evaluation management or follow-up of these lesions If utilized a CT computerized tomography scan is a special test using x-ray along with a computer to give detailed pictures of parts of the body An MRI magnetic resonance imaging is a special test using a strong magnetic field and radio frequency signals to give detailed pictures of parts of the body An x-ray shows a 2-dimensional picture while a CT scan or an MRI shows 3 dimensions
Each study course includes one week of treatment followed by three weeks of observation The length of the study is 6 months 6 courses for most participants Participants will return to the clinic twice a day for Days 2 - 5 for each month of participation and should expect to spend a total of about 6 hours a day at the clinic
Participants in this study will receive INGN 201 in two ways The first way will be by injection in the area of the lesion The second way will be by mouth rinse Vital signs will be checked each time before participants receive INGN 201 The injection will be given on the first day of each week of the course after a numbing anesthetic medication is applied to prevent discomfort
The mouth rinse will be given one time on the first day and two times on Days 2 - 5 of each course of INGN 201 The injection and rinse first day of each cycle or the two rinses Days 2 - 5 of each cycle will be separated by at least two hours There will be a 30 second rinse with 5 acetic acid a raspberry flavored vinegar-like liquid followed by a tap water rinse just before participants receive INGN 201 Participants will be asked to hold the INGN 201 in their mouth for 30 minutes Eating and drinking should be avoided for one hour after receiving the mouth rinse The injection and rinse series will be repeated on a monthly basis for a period of six months
Participants will be requested to have two biopsies small tissue samples of the premalignant lesion taken on Day 5 of the 1st and 6th courses These biopsies will contribute to the understanding of how the experimental agent works on pre-cancerous cells In particular the biopsies will help to determine if the experimental agent is effective in killing pre-cancerous cells this process is called apoptosis These studies will also determine if the gene therapy injections have been effective in delivering the gene p53 to the precancerous cells
Participants will be observed for three more weeks after the sixth course of treatment At the end of the study 28 days after the last dose of INGN 201 participants will have a physical exam including measurement of weight and vital signs Participants will have a medical history and blood and urine tests These tests are done to monitor the effects of the study treatment
Participants who develop severe side effects will be taken off study though they may continue to receive follow-up evaluations to monitor their health Participants will be counseled by their physician should the lesions progress to cancer during the study or follow up period After counseling participant may choose to have surgery to remove the precancerous lesions laser surgery or observation The participant will then be monitored closely
Study participants will be followed for five years and must agree to stay in contact with their personal doctor or the doctor responsible for this study even if they move after the study ends The participants personal doctor may be asked to provide information about any anticancer treatments received after the studys completion as well as information about the patients overall health
This is an investigational study This experimental use of human genes is an example of gene therapy This is the first time that adenovirus gene therapy has been used for a pre-cancerous condition This is the first study to use INGN 201 as a mouth rinse A total of 20 patients will be enrolled at M D Anderson A maximum of 51 subjects will be entered in this multi-center 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