LeukoplakiaPhase 2NCT00001698
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
A Phase 2 study testing Ketorolac Rinse in people with Leukoplakia and Periodontal Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukoplakia, Periodontal Disease
- What is being tested?
- Ketorolac Rinse
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1998to Jun 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have objective evidence of oral leukoplakia. This includes subjects who have had a previous diagnosis of head and neck or oral cancer, who are currently free of evidence of known cancer for at least three months.
- Patients must have bidimensionally measurable lesions.
- Patients must consent to serial photography and biopsy to document response to treatment.
- All patients old enough to give their own informed consent (greater than or equal to 18 years old) are eligible.
- Subjects must be excellent performance status (Performance Status 0-1).
- In addition, they must be otherwise medically fit in the opinion of the PI with no other uncontrolled medical conditions.
Who cannot join
- Patients with a hypersensitivity to aspirin, lidocaine or non-steroid anti-inflammatory agents or retinoids will be ineligible.
- Patients using antibiotics, steroids, NSAID, aspirin, probenecid or antihistamines for an extended regimen of at least 10 or more consecutive days, or any immunosuppressants, anticoagulants, dilantin, lithium, methotrexate, phenothiazines, investigational drugs with pharmacological activity that could compromise the test product safety during the 30 days immediately preceding the first treatment visit.
- Patients with serious or debilitating oral conditions that require extensive dental procedures in order to safely participate in this trial. This trial does not envision the need to do dental procedures (such as root canal or gingival procedure) in order to allow a potential participant to enroll on this study.
- Individuals with a social or psychiatric situation interfering with study compliance or an unwillingness to undergo the serial oral biopsies will be excluded.
- Patients with compromised respiratory function manifested by shortness of breath with mild exertion or dependency on supplemental oxygen.
- Patients with compromised cardiovascular status including poorly controlled angina or congestive heart failure.
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- ELIGIBILITY FOR ORAL IMAGING SUBSTUDY:
- Participation in this substudy requires that patients be enrolled in the parent trial.
- Subjects must have given their consent and signed supplemental informed consent for the pilot study involving oral imaging.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
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.
Read the 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.
- Conditions
- Leukoplakia, Periodontal Disease
- Being tested
- Ketorolac Rinse
- Keywords
- Chemoprevention, Direct Epithelial Delivery, Tobacco-induced Cancer, Field Cancerization
- Medical subject headings
- Leukoplakia, Periodontal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketorolac RinseDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startJun 1998
- Study completionJun 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LeukoplakiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 57 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001698
- Sponsor's protocol ID
- 980118
- Other IDs
- 98-C-0118
- Status last verified
- Jun 2004
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Cavanaugh PF Jr, Meredith MP, Buchanan W, Doyle MJ, Reddy MS, Jeffcoat MK. Coordinate production of PGE2 and IL-1 beta in the gingival crevicular fluid of adults with periodontitis: its relationship to alveolar bone loss and disruption by twice daily treatment with ketorolac tromethamine oral rinse. J Periodontal Res. 1998 Feb;33(2):75-82. doi: 10.1111/j.1600-0765.1998.tb02295.x.
PubMed 9553866Hong WK, Sporn MB. Recent advances in chemoprevention of cancer. Science. 1997 Nov 7;278(5340):1073-7. doi: 10.1126/science.278.5340.1073.
PubMed 9353183Potter M. Experimental plasmacytomagenesis in mice. Hematol Oncol Clin North Am. 1997 Apr;11(2):323-47. doi: 10.1016/s0889-8588(05)70434-2.
PubMed 9137973
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00001698
- Acronym / sponsor ID
- 980118
- Conditions
- Leukoplakia, Periodontal Disease
- Keywords
- Chemoprevention, Direct Epithelial Delivery, Tobacco-induced Cancer, Field Cancerization
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 1998
- Study completion
- Jun 2004
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must have objective evidence of oral leukoplakia. This includes subjects who have had a previous diagnosis of head and neck or oral cancer, who are currently free of evidence of known cancer for at least three months.
- Patients must have bidimensionally measurable lesions.
- Patients must consent to serial photography and biopsy to document response to treatment.
- All patients old enough to give their own informed consent (greater than or equal to 18 years old) are eligible.
- Subjects must be excellent performance status (Performance Status 0-1).
Key exclusion criteria (9 listed)
- Patients with a hypersensitivity to aspirin, lidocaine or non-steroid anti-inflammatory agents or retinoids will be ineligible.
- Patients using antibiotics, steroids, NSAID, aspirin, probenecid or antihistamines for an extended regimen of at least 10 or more consecutive days, or any immunosuppressants, anticoagulants, dilantin, lithium, methotrexate, phenothiazines, investigational drugs with pharmacological activity that could compromise the test product safety during the 30 days immediately preceding the first treatment visit.
- Patients with serious or debilitating oral conditions that require extensive dental procedures in order to safely participate in this trial. This trial does not envision the need to do dental procedures (such as root canal or gingival procedure) in order to allow a potential participant to enroll on this study.
- Individuals with a social or psychiatric situation interfering with study compliance or an unwillingness to undergo the serial oral biopsies will be excluded.
- Patients with compromised respiratory function manifested by shortness of breath with mild exertion or dependency on supplemental oxygen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketorolac Rinse | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9553866Cavanaugh PF Jr, Meredith MP, Buchanan W, Doyle MJ, Reddy MS, Jeffcoat MK. Coordinate production of PGE2 and IL-1 beta in the gingival crevicular fluid of adults with periodontitis: its relationship to alveolar bone loss and disruption by twice daily treatment with ketorolac tromethamine oral rinse. J Periodontal Res. 1998 Feb;33(2):75-82. doi: 10.1111/j.1600-0765.1998.tb02295.x.
- Background: PubMed 9353183Hong WK, Sporn MB. Recent advances in chemoprevention of cancer. Science. 1997 Nov 7;278(5340):1073-7. doi: 10.1126/science.278.5340.1073.
- Background: PubMed 9137973Potter M. Experimental plasmacytomagenesis in mice. Hematol Oncol Clin North Am. 1997 Apr;11(2):323-47. doi: 10.1016/s0889-8588(05)70434-2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketorolac Rinse in people with Leukoplakia and Periodontal Disease, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001698, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.