Ignite Creation Date:
2024-05-05 @ 5:04 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00386594
Status:
TERMINATED
Last Update Posted:
2009-01-21
First Post:
2006-10-08
Brief Title:
Pilot Study of Oral 852A for Elimination of High-Grade Dysplasia in Barretts Esophagus
Sponsor:
Rogers BH Gerald MD
Organization:
Rogers BH Gerald MD
Study Overview
Official Title:
None
Status:
TERMINATED
Status Verified Date:
2006-12
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:
Barretts esophagus with high-grade dysplasia is a premalignant condition caused by chronic reflux of gastric contents into the esophagus High-grade dysplasia is the same as carcinoma-in-situ If untreated patients with this condition are at high risk for developing cancer of the esophagus Cancer of the esophagus is a miserable disease that is difficult to treat and about 95 fatal after 5 years To prevent progession to cancer of the esophagus several interventions are available and they include surgery Photofrin photodynamic therapy endoscopic mucosal resection and endoscopic thermal therapy All of these modalities are uncomfortable expensive and have associated risks The oral agent 852A stimulates the innate immune system in such a way as to eliminate early cancer A similar dermatologic drugimiquimod is approved for treating the premalignant condition actinic keratosis If local therapy with imiquimod can eliminate a premalignant lesion in the skin a similar acting drug should be able to do the same for a premalignant lesion in the lining of the esophagus This study is designed to test that hypothesis
Detailed Description:
This study is to determine if a locally applied immune response modifier will eliminate high grade dysplasia in Barretts esophagus Barretts esophagus is a premalignant condition caused by chronic reflux of gastric contents into the lower esophagus Present practice is to do a periodic esophagoscopy on patients with Barretts esophagus and take biopsies in search of dysplasia If the pathologist reports low grade dysplasia the patient usually receives more intensive surveillance If the pathologist reports high grade dysplasia the patient and his physician are faced with a dilema High grade dysplasia is carcinoma in situ and there is a strong propensity for such patients to progess to frank carcinoma of the esophagus Carcinoma of the esophagus is a miserable disease which is difficult to treat and leads to death in about 95 of the cases at 5 years The present standard for patients with high grade dysplasia is to recommend esophagectomy Esophagectomy is a major surgical procedure with significant associated morbidity and mortality Porfimer sodiumPhotofrin photodynamic therapy is effective in eliminating high grade dysplasia in Barretts esophagus It has been approved by the FDA but it is not widely utilized because of its complexity and expense Other modalities such as endoscopic mucosal resection and endoscopic thermal ablation techiques are being studied Although endoscopic techniques are much safer than surgery they all are uncomfortable and carry some risk Many patients with Barretts esophagus are elderly and most with high grade dysplasia do not live long enough to develop cancer This fact has made some gastroenterolgists recommend intensive surveillance as an alternative to the above mentioned therapeutic modalities Intensive surveillance in this setting means endoscopy with biopsies every 3 months with specific therapy recommended only if frank cancer is found This study is based upon the fact that intensive surveillance is an acceptable way of following these patients The only difference is an oral agent will be added in hopes of getting rid of high grade dysplasia If high grade dysplasia could be eliminated by an oral medication it would be a quantum improvement over what we have The present belief is if high grade dysplasia is eliminated there would be no progression to cancer
852A is an immune response modifier being developed by 3M Pharmaceuticals It is thought to exert its therapeutic effect by simulating alpha interferon 852A is similar to the immune response modifier imiquimodAldara Imiquimod is presently approved by the precancerous dermatological condition actinic keratosis It is very effective Treatment is simply applying 5 imiquimod cream twice weekly to the skin lesion for 16 weeks It seems reasonable that if an immune response modifier will eliminate precancerous lesions of the skin by local application the same should be true for precancerous lesions of the esophagus In this study 852A will be swallowed to see whether it can eliminate high grade dysplasia from the esophagus
Entrance into the present study would be predicated on the confirmation of high grade dysplasia in Barretts esophagus If the prospective subject meets all of the inclusion and exclusion criteria set out in the protocol endoscopic ultrasound of the esophagus would be done If endoscopic ultrasound shows no invasion into the submucosa the patient would be asked to sign an informed consent Once entered into the sudy the subject would be given the study drug twice weekly 3-4 days apart for 8 weeks 852A will be supplied in sterile vials by 3M Pharmaceuticals Five mg of 852A will be mixed with sterile 5 dextrose in water to give a final volume of 30 ml The patient will promply swallow the study drug after it is mixed The subject will then assume a recumbent position for 30 minutes in hopes that the medication will stay in contact with the mucosa of the esophagus long enough to get an effect All doses of the study medication will be given in the principal investigators clinic After the first dose is given that patient will stay in the clinic under observation for 4 hours Observation includes taking the temperature pulse and blood pressure every hour If there are no adverse effects after the first dose the observation period after subsequent doses will reduced to one hour Laboratory tests will be repeated 124 and 8 weeks after the first dose is given As set out in the study protocol if the patient has any significant adverse event or laboratory deviation the subject would be dropped from the study Throughout the study the subjects will be treated with a double dose of a proton pump inhibitor to control gastric acid reflux
After 8 weeks of therapy the study medication will be stopped Four weeks thereafter and 12 weeks from the beginning repeat endosocpy with biopsies will be done If biopsies show no residual high grade dysplasia the patient will be continued in an intensive surveillance program Intensive surveillance means endoscopy with biopsies every 3 months for 1 year then every 6 months for 1 year then yearly for 3 more years If high grade dysplsia persists after 8 weeks of treatment or cancer is found the patient would be referred for conventional therapy Likewise if high grade dysplsia recurs or cancer is found during the intensive surveillance program the subject will be referred for conventional therapy
852A is an immune response modifier being developed by 3M Pharmaceuticals It is thought to exert its therapeutic effect by simulating alpha interferon 852A is similar to the immune response modifier imiquimodAldara Imiquimod is presently approved by the precancerous dermatological condition actinic keratosis It is very effective Treatment is simply applying 5 imiquimod cream twice weekly to the skin lesion for 16 weeks It seems reasonable that if an immune response modifier will eliminate precancerous lesions of the skin by local application the same should be true for precancerous lesions of the esophagus In this study 852A will be swallowed to see whether it can eliminate high grade dysplasia from the esophagus
Entrance into the present study would be predicated on the confirmation of high grade dysplasia in Barretts esophagus If the prospective subject meets all of the inclusion and exclusion criteria set out in the protocol endoscopic ultrasound of the esophagus would be done If endoscopic ultrasound shows no invasion into the submucosa the patient would be asked to sign an informed consent Once entered into the sudy the subject would be given the study drug twice weekly 3-4 days apart for 8 weeks 852A will be supplied in sterile vials by 3M Pharmaceuticals Five mg of 852A will be mixed with sterile 5 dextrose in water to give a final volume of 30 ml The patient will promply swallow the study drug after it is mixed The subject will then assume a recumbent position for 30 minutes in hopes that the medication will stay in contact with the mucosa of the esophagus long enough to get an effect All doses of the study medication will be given in the principal investigators clinic After the first dose is given that patient will stay in the clinic under observation for 4 hours Observation includes taking the temperature pulse and blood pressure every hour If there are no adverse effects after the first dose the observation period after subsequent doses will reduced to one hour Laboratory tests will be repeated 124 and 8 weeks after the first dose is given As set out in the study protocol if the patient has any significant adverse event or laboratory deviation the subject would be dropped from the study Throughout the study the subjects will be treated with a double dose of a proton pump inhibitor to control gastric acid reflux
After 8 weeks of therapy the study medication will be stopped Four weeks thereafter and 12 weeks from the beginning repeat endosocpy with biopsies will be done If biopsies show no residual high grade dysplasia the patient will be continued in an intensive surveillance program Intensive surveillance means endoscopy with biopsies every 3 months for 1 year then every 6 months for 1 year then yearly for 3 more years If high grade dysplsia persists after 8 weeks of treatment or cancer is found the patient would be referred for conventional therapy Likewise if high grade dysplsia recurs or cancer is found during the intensive surveillance program the subject will be referred for conventional therapy
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