Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001698
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
1999-11-03
Brief Title:
Randomized Double Blind Placebo-Controlled Phase IIB Trial of Ketorolac Mouth Rinse Evaluating the Effect of Cyclooxygenase Inhibition on Oropharyngeal Leukoplakia Collaborative Study of the NCI NIDCD and the NIDCR
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Randomized Double Blind Placebo-Controlled Phase IIB Trial of Ketorolac Mouth Rinse Evaluating the Effect of Cyclooxygenase Inhibition on Oropharyngeal Leukoplakia Collaborative Study of the NCI NIDCD and the NIDCR
Status:
COMPLETED
Status Verified Date:
2004-06
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:
In Phase II trials treatment with ketorolac tromethamine oral rinse has been shown to block periodontal disease progression even in the absence of standard clinical intervention such as scaling and root planing which is routinely done to reduce the periodontal pathogen load that is driving the local destructive host inflammatory response Resolution of periodontal disease has a favorable effect on normalizing the cellular and biochemical indices of inflammation as reflected by histological changes as well as the levels of prostaglandin E2 PGE2 and interleukin I beta IL-1beta In this trial we will prospectively evaluate if eliminating the inflammatory process via inhibition of PGE2 biosynthesis in the oral cavity has a favorable impact on reversing oropharyngeal leukoplakia To test this hypothesis up to 57 prospectively identified individuals with objective findings of oropharyngeal leukoplakia will be randomized to receive either a mouth rinse containing ketorolac or placebo Ketorolac is a 7-fold selective inhibitor of cyclooxygenase-2 Cox-2 which has been designed for local delivery to maximize the drug exposure to critical oral target tissues while minimizing gastric and systemic exposure to the drug All responses will be determined at the three month completion of trial using the response criteria developed at MD Anderson Cancer Center The drug will be given for three months and then all the patients will be followed for one additional month off all oral treatment to observe for late side effects Based on the analysis of oral exam and photographically documented change in the pretreatment area of leukoplakia the response of all patients will be determined
The evaluation of the outcome will include a measurable secondary endpoint consisting of an assessment of histological change as determined by serial punch biopsies of the oral cavity In addition a panel of carcinogenesis and inflammatory markers will be serially measured at baseline at one month follow up or at study conclusion In the residual tissue other bioassays will be evaluated to determine their suitability as intermediate endpoint markers The purpose of this study is a preliminary evaluation of the effectiveness of ketorolac as a potential chemoprevention agent for oropharyngeal cancer If ketorolac administration in this preliminary Phase IIB trial is associated with reversal of leukoplakia then a definitive Phase III chemoprevention trial with a cancer reduction endpoint most likely in a cooperative group-type setting may be the next validation step
The evaluation of the outcome will include a measurable secondary endpoint consisting of an assessment of histological change as determined by serial punch biopsies of the oral cavity In addition a panel of carcinogenesis and inflammatory markers will be serially measured at baseline at one month follow up or at study conclusion In the residual tissue other bioassays will be evaluated to determine their suitability as intermediate endpoint markers The purpose of this study is a preliminary evaluation of the effectiveness of ketorolac as a potential chemoprevention agent for oropharyngeal cancer If ketorolac administration in this preliminary Phase IIB trial is associated with reversal of leukoplakia then a definitive Phase III chemoprevention trial with a cancer reduction endpoint most likely in a cooperative group-type setting may be the next validation step
Detailed Description:
In Phase II trials treatment with ketorolac tromethamine oral rinse has been shown to block periodontal disease progression even in the absence of standard clinical intervention such as scaling and root planing which is routinely done to reduce the periodontal pathogen load that is driving the local destructive host inflammatory response Resolution of periodontal disease has a favorable effect on normalizing the cellular and biochemical indices of inflammation as reflected by histological changes as well as the levels of prostaglandin E2 PGE2 and interleukin I beta IL-1beta In this trial we will prospectively evaluate if eliminating the inflammatory process via inhibition of PGE2 biosynthesis in the oral cavity has a favorable impact on reversing oropharyngeal leukoplakia To test this hypothesis up to 57 prospectively identified individuals with objective findings of oropharyngeal leukoplakia will be randomized to receive either a mouth rinse containing ketorolac or placebo Ketorolac is a 7-fold selective inhibitor of cyclooxygenase-2 Cox-2 which has been designed for local delivery to maximize the drug exposure to critical oral target tissues while minimizing gastric and systemic exposure to the drug All responses will be determined at the three month completion of trial using the response criteria developed at MD Anderson Cancer Center The drug will be given for three months and then all the patients will be followed for one additional month off all oral treatment to observe for late side effects Based on the analysis of oral exam and photographically documented change in the pretreatment area of leukoplakia the response of all patients will be determined
The evaluation of the outcome will include a measurable secondary endpoint consisting of an assessment of histological change as determined by serial punch biopsies of the oral cavity In addition a panel of carcinogenesis and inflammatory markers will be serially measured at baseline at one month follow up or at study conclusion In the residual tissue other bioassays will be evaluated to determine their suitability as intermediate endpoint markers The purpose of this study is a preliminary evaluation of the effectiveness of ketorolac as a potential chemoprevention agent for oropharyngeal cancer If ketorolac administration in this preliminary Phase IIB trial is associated with reversal of leukoplakia then a definitive Phase III chemoprevention trial with a cancer reduction endpoint most likely in a cooperative group-type setting may be the next validation step
The evaluation of the outcome will include a measurable secondary endpoint consisting of an assessment of histological change as determined by serial punch biopsies of the oral cavity In addition a panel of carcinogenesis and inflammatory markers will be serially measured at baseline at one month follow up or at study conclusion In the residual tissue other bioassays will be evaluated to determine their suitability as intermediate endpoint markers The purpose of this study is a preliminary evaluation of the effectiveness of ketorolac as a potential chemoprevention agent for oropharyngeal cancer If ketorolac administration in this preliminary Phase IIB trial is associated with reversal of leukoplakia then a definitive Phase III chemoprevention trial with a cancer reduction endpoint most likely in a cooperative group-type setting may be the next validation step
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 |
|---|---|---|---|
| 98-C-0118 | None | None | None |