Ignite Creation Date:
2024-05-05 @ 7:11 PM
Last Modification Date:
2024-10-26 @ 9:45 AM
Study NCT ID:
NCT00628784
Status:
UNKNOWN
Last Update Posted:
2008-07-24
First Post:
2008-02-25
Brief Title:
Endoesophageal Cryotherapy For Ablating Barretts Esophagus and Early Stage Esophageal Cancer
Sponsor:
Walter Reed Army Medical Center
Organization:
Walter Reed Army Medical Center
Study Overview
Official Title:
Endoesophageal Cryotherapy A New Technique For Ablating Barretts Esophagus And Early Stage Esophageal Cancer
Status:
UNKNOWN
Status Verified Date:
2008-07
Last Known Status:
RECRUITING
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 this prospective single center study up to 25 patients with Barretts esophagus with LGD or no dysplasia Group 1 25 patients with HGDIMCA Group 2 25 patients with esophageal carcinoma confined to the esophageal wall Group 3 and 25 patients with severe esophageal squamous dysplasia Group 4 will be treated with endoscopic cryotherapy This study is single arm and no blinding will be utilized Interim analysis of the data will be reviewed with a DCI statistician after 14 patients in each group have been treated with cryotherapy and if safety and efficacy is documented to that point in time we will request the ability to extend the enrollment to a maximum allowable amount of 25 patients per group The proposed study duration is seven years allowing two years for patient enrollment and 5 years for post treatment follow-up Study duration per patient will total approximately six years
Patients with Barretts esophagus with no dysplasia or low grade dysplasia group 1 will be treated with cryotherapy at six week intervals until Barretts mucosa is ablated or six treatments are administered Patients with Barretts HGD and IMCA or severe esophageal squamous dysplasia groups 2 and 4 will be treated with cryotherapy at six-week intervals until Barretts mucosa is ablated or six treatments are administered More advanced mass lesions are typically more difficult to eradicate with ablative therapies and may progress faster than patients with IMCA therefore patients with more advanced cancer group 3 will be treated every 2 weeks until the lesion is eradicated up to eight treatments
After cryotherapy treatment is complete ie the esophagus has re-epithelialized with normal squamous epithelium for Groups 1 2 4 and the tumor is locally controlledabsent in Group 3 patients will be assessed by endoscopy and biopsy every three months for one year every six months for two years then annually for two years flow sheet - appendix 1 study schedule - appendix 2
Patients with Barretts esophagus with no dysplasia or low grade dysplasia group 1 will be treated with cryotherapy at six week intervals until Barretts mucosa is ablated or six treatments are administered Patients with Barretts HGD and IMCA or severe esophageal squamous dysplasia groups 2 and 4 will be treated with cryotherapy at six-week intervals until Barretts mucosa is ablated or six treatments are administered More advanced mass lesions are typically more difficult to eradicate with ablative therapies and may progress faster than patients with IMCA therefore patients with more advanced cancer group 3 will be treated every 2 weeks until the lesion is eradicated up to eight treatments
After cryotherapy treatment is complete ie the esophagus has re-epithelialized with normal squamous epithelium for Groups 1 2 4 and the tumor is locally controlledabsent in Group 3 patients will be assessed by endoscopy and biopsy every three months for one year every six months for two years then annually for two years flow sheet - appendix 1 study schedule - appendix 2
Detailed Description:
Baseline evaluation will include the following all are considered standard of care except 8
1 Informed consent
2 Evaluation of inclusionexclusion criteria
3 Demographics- date of birth age gender ethnicity
4 Medical history and physical exam
5 Imaging groups 2 3 and 4 i CT scan of the chest and abdomen with oral and intravenous contrast if not allergic ii Endoscopic Ultrasound with evaluation of the esophageal wall and mediastinum and upper abdomen for evidence of abnormal lymph nodes Suspicious lymph nodes round hypoechoic homogeneous 5mm will undergo EUS-guided fine needle aspiration if appropriate as deemed by the principal investigator
6 Pathology review groups 2 and 4 - two independent reviewers including at least one from the WRAMC Pathology Department will review the pathology slides from esophageal biopsies This review will serve to confirm the diagnosis of Barretts esophagus with high grade dysplasia andor IMCA for agreement of the diagnosis of adenocarcinoma and the degree of dysplasia
7 Presentation at Tumor Board prior to entering the protocol groups 2 3 and 4
8 Dysphagia score see Appendix 4 is for research purposes
Prior to cryotherapy
As part of the research protocol all patients will be treated with high dose proton pump inhibitor PPI lansoprazole 30mg esomeprazole 40mg pantoprazole 40mg omeprazole 40mg or rabeprazole 40mg BID for maximal acid suppression until complete ablation is achieved or the patient exits the study All of these agents are considered equally effective at the doses listed with no one agent considered superior Treatment with these research doses will begin at least one week prior to the first cryotherapy session Pre-enrollment standard doses of PPI will be restarted once the patient enters the surveillance phase or exits the study Care will be taken to avoid if possible any potentially toxic medications to the esophageal mucosa ie non-steroidal anti-inflammatory drugs bisphosphonates potassium supplements
EGDCryotherapy Patients will be scheduled for EGD with cryotherapy on designated days when support for the cryotherapy device is available according to the study timeline Appendix 2 A commitment from the CSA Medical Inc Baltimore MD will provide technical support for sessions to allow patients timely treatment
Patients will prepare for EGD in the standard fashion using an overnight fast with only sips of clear liquids and required medications allowed up to 2 hours before the procedure Patients will be interviewed prior to the procedure using a standardized questionnaire Appendix 3 This questionnaire will assess overall sense of well-being general state of health ability to perform activities of daily living and ability to eat It will specifically solicit symptoms of chest pain irregular heart rate shortness of breath dysphagia or odynophagia A dysphagia score will also be measured appendix 4
Moderate sedation with intravenous meperidine or fentanyl and midazolam will be administered and staff investigators will perform the EGD using a therapeutic upper endoscope with adherence to standard protocol A 14 to 18 French nasogastric tube which has been modified with decompression ports spanning the distal 12 inches of the tube to allow decompression of both the stomach and the esophagus will be placed into the stomach under direct visualization This is connected to continuous suction to allow decompression during the cryotherapy procedure During the procedure an assistant will monitor and record the heart rate blood pressure and oxygen saturation per WRAMC moderate sedation guidelines
All subjects will be treated with narcotic analgesics and anti-emetics as needed after each procedure
Groups 1 2 and 4 At the first procedure the most proximal edge of the squamocolumnar junction SCJ and the tips of the gastric folds gastroesophageal junction of GEJ will be marked with a submucosal tattoo of India ink SPOT GI Supply Camp Hill PA using a standard sclerotherapy needle if not already performed The ink tattoo will guide measurement of response to ablation and sampling the neo-squamous segment for residual Barretts during follow up exams For severe esophageal squamous dysplasia the tattoo will be applied at the proximal and distal margins of the dysplastic area If not allergic to iodine Lugols solution will be used to stain the squamous mucosa during the exam to outline the area of severe squamous dysplasia and guide the tattoo placement Lugols is chosen since normal squamous but not dysplasia or carcinoma stains with this vital stain These marks are placed for research purposes only and help to ensure that accurate measurements to assess the change of Barretts segment with therapy are recorded 30 The location of the squamocolumnar junction SCJ the esophagogastric junction EGJ and diaphragmatic hiatus DH will be documented in terms of centimeters from the incisors Any islands of squamous tissue within the Barretts segment will be photographed measured and recorded If the SCJ is not well visualized chromoendoscopy with Lugols solution which highlights the squamous epithelium will be performed
The cryocatheter is passed into the therapeutic channel of the endoscope and extended one cm beyond the distal tip of the scope Liquid nitrogen is sprayed through the cryocatheter which causes a white frost cryoburn on the adjacent mucosa The most distal aspect of the Barretts esophagus segment is treated first and the endoscope is slowly withdrawn proximally maneuvering the tip of the cryocatheter such that the cryoburn is extended to paint a white frost cryoburn circumferentially The spray will be applied for duration of 10 seconds as measured by the integrated device timer During each cryotherapy session the process will be repeated up to four times in piecemeal fashion such that for any given area treated it will be maintained in a frozen state for a total of 40 seconds A frozen state will be defined as mucosa appearing white
At the completion of the endoscopic procedure the patients are monitored in our recovery area until completely awake alert and able to be discharged according to our standard conscious sedation policy Following discharge from the endoscopy suite patients will be contacted in one week by telephone to assess for any immediate complications A questionnaire will be completed by the study physician or nurse appendix 3 Patients will be seen the same day in the clinic or endoscopy center for any serious concerns patient or study personnel
Patients will return in 6 weeks groups 1 2 and 4 for reassessment with a repeat EGD and cryotherapy for residual Barretts mucosa The interview questionnaire and dysphagia score will be repeated before each EGD The location of the SCJ the EGJ and DH and dysplastic region will be recorded and photographed to characterize the precise size and location of any islands of squamous tissue within the Barretts segment If there is gross evidence of mucosal injury due to the previous cryotherapy any mucosal break including erosions tears or ulcers the procedure will be terminated and further ablation will be held for an additional 2 weeks If there is no gross evidence of esophageal mucosal injury cryotherapy will be repeated The process will continue until complete ablation of the Barretts mucosa has been achieved or the maximum number of treatment sessions has been performed 8 treatments total
When it appears endoscopically that all or nearly all of the mucosa has been replaced with normal appearing squamous mucosa a biopsy or several biopsies may be taken at the discretion of the endoscopist of any suspicious areas to confirm that cryotherapy has been completed When such quick look biopsies have been taken no cryotherapy will be performed that day
If the pathology results return revealing sub-squamous intestinal metaplasia or dysplasia cryotherapy may be resumed two weeks after the biopsies had been taken to allow adequate time for the mucosa to have healed If the biopsy confirms resolution the patient will then be scheduled for post-cryotherapy surveillance
Biopsies taken during these endoscopies will be used only for the clinical purpose of assessing the patients histologic response to cryotherapy As such no excess tissue will be collected or stored for any purposes
Group 3
Group 3 patients will undergo cryotherapy with intent to ablate the neoplasia Group 3 patients with long segment Barretts esophagus will undergo ablation of only the nodular areas andor mass lesions Flat Barretts will not be treated The mass lesion will be treated in its entirety until frozen or up to 20 seconds This will be repeated for a total treatment time of 60 seconds
Follow up endoscopy to allow repeat treatment with cryotherapy will be every two weeks until the lesion is eradicated or is treated up to 8 times whichever comes first These patients are being offered more aggressive therapy every 2 weeks rather than every 6 weeks due to the presence of more advanced disease Treatment will be withheld for evidence of active ulceration and will not be resumed until this has healed When it appears endoscopically that the cancer has been eradicated and all or nearly all of the mucosa has been replaced with normal appearing squamous mucosa a biopsy or several biopsies may be taken at the discretion of the endoscopist of any suspicious areas to confirm that cryotherapy has been completed When such quick look biopsies have been taken no cryotherapy will be performed that day If the pathology results return revealing sub-squamous intestinal metaplasia dysplasia or cancer cryotherapy may be resumed If the biopsy confirms resolution the patient will then be scheduled for post-cryotherapy surveillance
Biopsies taken during these endoscopies will be used only for the clinical purpose of assessing the patients histologic response to cryotherapy As such no excess tissue will be collected or stored for any purposes No blood will be drawn for this study
The initial EGD procedures are estimated to require up to 45 minutes to perform due to the possible need to perform Lugols staining andor India ink marking of the esophagus Subsequent re-treatment EGDs are estimated to require no more than 30 minutes to perform An EGD that reveals healing where only quick look biopsies are taken will take no more than 10 minutes to perform
1 Informed consent
2 Evaluation of inclusionexclusion criteria
3 Demographics- date of birth age gender ethnicity
4 Medical history and physical exam
5 Imaging groups 2 3 and 4 i CT scan of the chest and abdomen with oral and intravenous contrast if not allergic ii Endoscopic Ultrasound with evaluation of the esophageal wall and mediastinum and upper abdomen for evidence of abnormal lymph nodes Suspicious lymph nodes round hypoechoic homogeneous 5mm will undergo EUS-guided fine needle aspiration if appropriate as deemed by the principal investigator
6 Pathology review groups 2 and 4 - two independent reviewers including at least one from the WRAMC Pathology Department will review the pathology slides from esophageal biopsies This review will serve to confirm the diagnosis of Barretts esophagus with high grade dysplasia andor IMCA for agreement of the diagnosis of adenocarcinoma and the degree of dysplasia
7 Presentation at Tumor Board prior to entering the protocol groups 2 3 and 4
8 Dysphagia score see Appendix 4 is for research purposes
Prior to cryotherapy
As part of the research protocol all patients will be treated with high dose proton pump inhibitor PPI lansoprazole 30mg esomeprazole 40mg pantoprazole 40mg omeprazole 40mg or rabeprazole 40mg BID for maximal acid suppression until complete ablation is achieved or the patient exits the study All of these agents are considered equally effective at the doses listed with no one agent considered superior Treatment with these research doses will begin at least one week prior to the first cryotherapy session Pre-enrollment standard doses of PPI will be restarted once the patient enters the surveillance phase or exits the study Care will be taken to avoid if possible any potentially toxic medications to the esophageal mucosa ie non-steroidal anti-inflammatory drugs bisphosphonates potassium supplements
EGDCryotherapy Patients will be scheduled for EGD with cryotherapy on designated days when support for the cryotherapy device is available according to the study timeline Appendix 2 A commitment from the CSA Medical Inc Baltimore MD will provide technical support for sessions to allow patients timely treatment
Patients will prepare for EGD in the standard fashion using an overnight fast with only sips of clear liquids and required medications allowed up to 2 hours before the procedure Patients will be interviewed prior to the procedure using a standardized questionnaire Appendix 3 This questionnaire will assess overall sense of well-being general state of health ability to perform activities of daily living and ability to eat It will specifically solicit symptoms of chest pain irregular heart rate shortness of breath dysphagia or odynophagia A dysphagia score will also be measured appendix 4
Moderate sedation with intravenous meperidine or fentanyl and midazolam will be administered and staff investigators will perform the EGD using a therapeutic upper endoscope with adherence to standard protocol A 14 to 18 French nasogastric tube which has been modified with decompression ports spanning the distal 12 inches of the tube to allow decompression of both the stomach and the esophagus will be placed into the stomach under direct visualization This is connected to continuous suction to allow decompression during the cryotherapy procedure During the procedure an assistant will monitor and record the heart rate blood pressure and oxygen saturation per WRAMC moderate sedation guidelines
All subjects will be treated with narcotic analgesics and anti-emetics as needed after each procedure
Groups 1 2 and 4 At the first procedure the most proximal edge of the squamocolumnar junction SCJ and the tips of the gastric folds gastroesophageal junction of GEJ will be marked with a submucosal tattoo of India ink SPOT GI Supply Camp Hill PA using a standard sclerotherapy needle if not already performed The ink tattoo will guide measurement of response to ablation and sampling the neo-squamous segment for residual Barretts during follow up exams For severe esophageal squamous dysplasia the tattoo will be applied at the proximal and distal margins of the dysplastic area If not allergic to iodine Lugols solution will be used to stain the squamous mucosa during the exam to outline the area of severe squamous dysplasia and guide the tattoo placement Lugols is chosen since normal squamous but not dysplasia or carcinoma stains with this vital stain These marks are placed for research purposes only and help to ensure that accurate measurements to assess the change of Barretts segment with therapy are recorded 30 The location of the squamocolumnar junction SCJ the esophagogastric junction EGJ and diaphragmatic hiatus DH will be documented in terms of centimeters from the incisors Any islands of squamous tissue within the Barretts segment will be photographed measured and recorded If the SCJ is not well visualized chromoendoscopy with Lugols solution which highlights the squamous epithelium will be performed
The cryocatheter is passed into the therapeutic channel of the endoscope and extended one cm beyond the distal tip of the scope Liquid nitrogen is sprayed through the cryocatheter which causes a white frost cryoburn on the adjacent mucosa The most distal aspect of the Barretts esophagus segment is treated first and the endoscope is slowly withdrawn proximally maneuvering the tip of the cryocatheter such that the cryoburn is extended to paint a white frost cryoburn circumferentially The spray will be applied for duration of 10 seconds as measured by the integrated device timer During each cryotherapy session the process will be repeated up to four times in piecemeal fashion such that for any given area treated it will be maintained in a frozen state for a total of 40 seconds A frozen state will be defined as mucosa appearing white
At the completion of the endoscopic procedure the patients are monitored in our recovery area until completely awake alert and able to be discharged according to our standard conscious sedation policy Following discharge from the endoscopy suite patients will be contacted in one week by telephone to assess for any immediate complications A questionnaire will be completed by the study physician or nurse appendix 3 Patients will be seen the same day in the clinic or endoscopy center for any serious concerns patient or study personnel
Patients will return in 6 weeks groups 1 2 and 4 for reassessment with a repeat EGD and cryotherapy for residual Barretts mucosa The interview questionnaire and dysphagia score will be repeated before each EGD The location of the SCJ the EGJ and DH and dysplastic region will be recorded and photographed to characterize the precise size and location of any islands of squamous tissue within the Barretts segment If there is gross evidence of mucosal injury due to the previous cryotherapy any mucosal break including erosions tears or ulcers the procedure will be terminated and further ablation will be held for an additional 2 weeks If there is no gross evidence of esophageal mucosal injury cryotherapy will be repeated The process will continue until complete ablation of the Barretts mucosa has been achieved or the maximum number of treatment sessions has been performed 8 treatments total
When it appears endoscopically that all or nearly all of the mucosa has been replaced with normal appearing squamous mucosa a biopsy or several biopsies may be taken at the discretion of the endoscopist of any suspicious areas to confirm that cryotherapy has been completed When such quick look biopsies have been taken no cryotherapy will be performed that day
If the pathology results return revealing sub-squamous intestinal metaplasia or dysplasia cryotherapy may be resumed two weeks after the biopsies had been taken to allow adequate time for the mucosa to have healed If the biopsy confirms resolution the patient will then be scheduled for post-cryotherapy surveillance
Biopsies taken during these endoscopies will be used only for the clinical purpose of assessing the patients histologic response to cryotherapy As such no excess tissue will be collected or stored for any purposes
Group 3
Group 3 patients will undergo cryotherapy with intent to ablate the neoplasia Group 3 patients with long segment Barretts esophagus will undergo ablation of only the nodular areas andor mass lesions Flat Barretts will not be treated The mass lesion will be treated in its entirety until frozen or up to 20 seconds This will be repeated for a total treatment time of 60 seconds
Follow up endoscopy to allow repeat treatment with cryotherapy will be every two weeks until the lesion is eradicated or is treated up to 8 times whichever comes first These patients are being offered more aggressive therapy every 2 weeks rather than every 6 weeks due to the presence of more advanced disease Treatment will be withheld for evidence of active ulceration and will not be resumed until this has healed When it appears endoscopically that the cancer has been eradicated and all or nearly all of the mucosa has been replaced with normal appearing squamous mucosa a biopsy or several biopsies may be taken at the discretion of the endoscopist of any suspicious areas to confirm that cryotherapy has been completed When such quick look biopsies have been taken no cryotherapy will be performed that day If the pathology results return revealing sub-squamous intestinal metaplasia dysplasia or cancer cryotherapy may be resumed If the biopsy confirms resolution the patient will then be scheduled for post-cryotherapy surveillance
Biopsies taken during these endoscopies will be used only for the clinical purpose of assessing the patients histologic response to cryotherapy As such no excess tissue will be collected or stored for any purposes No blood will be drawn for this study
The initial EGD procedures are estimated to require up to 45 minutes to perform due to the possible need to perform Lugols staining andor India ink marking of the esophagus Subsequent re-treatment EGDs are estimated to require no more than 30 minutes to perform An EGD that reveals healing where only quick look biopsies are taken will take no more than 10 minutes to perform
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