Ignite Creation Date:
2024-05-06 @ 1:39 AM
Last Modification Date:
2024-10-26 @ 11:07 AM
Study NCT ID:
NCT01868139
Status:
TERMINATED
Last Update Posted:
2022-03-07
First Post:
2013-03-30
Brief Title:
Spray Cryotherapy for Esophageal Cancer ICE-CANCER
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
A Phase II Multi-Center Study of Interventional Spray Cryotherapy for Early-Stage Esophageal Cancer ICE-CANCER
Status:
TERMINATED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
insufficient accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ICE-CANCER
Brief Summary:
The goal of this study is to evaluate the safety and efficacy of endoscopic spray cryotherapy using the CSA Medical Inc truFreeze System for patients with previously untreated early-stage cancer T1a N0 M0 who are ineligible or refuse conventional therapy including surgery chemotherapy radiation therapy and endoscopic resection
It is hypothesized that one of the two following outcomes will occur
1 Complete response to therapy complete tumor eradication confirmed through histologic examination of biopsy specimens from the targeted esophageal tissue site
2 Stable disease tumor remission is not attained but disease progression is halted
It is hypothesized that one of the two following outcomes will occur
1 Complete response to therapy complete tumor eradication confirmed through histologic examination of biopsy specimens from the targeted esophageal tissue site
2 Stable disease tumor remission is not attained but disease progression is halted
Detailed Description:
Background
Endoscopic modalities have been reported to be effective in definitive treatment of early stage esophageal cancer A study comparing endoscopic treatment to surgery in early esophageal cancer using the SEER Surveillance Epidemiology and End Results database showed no difference in the relative hazard of death from esophageal cancer between the two groups The primary endoscopic therapies used in this study were endoscopic mucosal resection EMR and photodynamic therapy PDT Estimated 1 and 3 year survival in this study were 92 and 75 in the endoscopic arm and 92 and 82 in the surgical arm EMR endoscopic excision of superficial cancer has also been shown to be highly effective in mucosal tumors in single center studies Low-risk lesions defined as flat or raised mucosal tumors 2 cm or less that are well-or moderately-differentiated without lymphovascular invasion demonstrate complete response was seen in 966 of patients with 5 year survival of 84 However high-risk lesions defined as greater than 2 cm poorly-differentiated flat-ulcerated or invading into the submucosa have a complete remission rate of only 59
Endoscopic resection is not possible in all mucosal cancers Some cancers are not visible endoscopically but detected only by endoscopic biopsy In other cases the EMR cannot be done due to scarring from previous resection or other therapy especially external beam radiation Management of these cases is problematic PDT using porfimer sodium has been extensively studied for Barretts esophagus with high-grade dysplasia however studies of PDT for early stage esophageal cancer are limited In a recent single site study using PDT and EMR for mucosal cancers overall survival was comparable to a group treated with esophagectomy at the same center with estimated 1 and 3 year survival of 98 and 95 PDT was used in 43 in combination with EMR in the endoscopic treatment group Recurrent carcinoma was detected in 16 of endoscopically treated patients All recurrences were intramucosal cancers with all but one managed by EMR Overall endoscopic treatment was well-tolerated However side effects of PDT are common and include photosensitivity esophageal stricture chest pain nausea vomiting and fever In the US PDT is no longer commonly used in the esophagus due to availability of alternative treatment modalities with less cost and side effects
Endoscopic spray cryotherapy with liquid nitrogen has emerged as an alternative treatment in stage I esophageal cancer in those not suitable for other therapies A recent retrospective review at 10 US centers assessed outcomes in seventy-nine patients Patients included those with esophageal carcinoma who failed refused or were ineligible for conventional therapy including chemotherapy radiation combination chemotherapy and radiation esophagectomy and endoscopic mucosal resection The majority of patients 76 had tumor stage T1N0M0 with mean tumor length of 4 cm All patients were treated with liquid nitrogen spray cryotherapy and forty-nine patients completed treatment Complete response of luminal disease occurred in 612 including 18 of 24 75 with mucosal cancer Follow-up averaged 106 to 115 months and no serious adverse events were reported Longer term follow-up was reported recently in abstract form Complete response was seen in 92 of patients with mucosal cancer with median follow-up of 28 months and overall estimated survival at 1 and 3 years of 98 and 92 respectively
Published studies have demonstrated spray cryotherapy to be safe and well-tolerated with low overall complication rates Tolerance of the procedure is very good All procedures are performed on an outpatient basis Primary side effects include chest pain dysphagia and odynophagia reported in about half of all procedures Mean duration of symptoms was 36 days and many patients had no side effects after treatment Serious adverse events were rare Gastric perforation occurred in one patient with Marfans syndrome Benign esophageal stricture was reported in 13 of patients treated for cancer with previous esophageal narrowing noted in 910 In combination with its relative cost-effectiveness and minimal invasiveness endoscopic spray cryotherapy is an appealing option for those with stage I esophageal cancer who are ineligible or refuse conventional therapies
Study Device truFreezeTM System CSA Medical Inc Baltimore MD
Study Objective The objective of this study is to evaluate the safety and efficacy of endoscopic spray cryotherapy using the CSA Medical Inc truFreeze System for patients with early-stage esophageal cancer T1a N0 M0 who are ineligible or refuse conventional therapy including surgery chemotherapy radiation therapy and endoscopic resection
Study Design Multi-center phase II study
Study Population Patients with early-stage esophageal cancer stage T1aN0M0
Study Duration It is estimated that enrollment will take approximately two years Each subject will remain in the study for up to one-year of treatment and for three years post-treatment It is expected to take five years to collect all required data for this study
Sample size 40
Treatment
Participant receives liquid nitrogen spray cryotherapy every 4 - 8 weeks x no more than 8 cycles Those with complete response to therapy will proceed to surveillance Those with stable or responding disease will continue with cryotherapy Those with progression of disease will discontinue protocol For responding or stable disease after 8 cycles continue treatment beyond 8 cycles until tumor progression or unacceptable toxicity Discontinue protocol therapy for disease progression or unacceptable toxicity
Follow-Up Evaluations and Data Collection
Patients will return for surveillance EGD esophagogastroduodenoscopy procedures with biopsies at 3 6 9 12 18 24 30 and 36 months 4 weeks after the last cryotherapy treatment An estimate of tumor size and response compared to baseline will be made at each endoscopy Biopsies will be performed using large capacity forceps In the area where tumor was present biopsies will be taken every 1 cm in each quadrant Directed biopsies will be performed in any areas that appear suspicious for cancer
CT scan of the chest abdomen and pelvis with oral and intravenous contrast if possible will be performed every 6 months during the follow-up period Full body PETCT may also be performed instead of CT scanning
Endoscopic ultrasound will be performed 6 months after treatment completion to assess for lymphadenopathy
At the conclusion of this protocol regardless of the outcome patients will continue to require periodic surveillance endoscopies for re-emergence of esophageal cancer consistent with the standard surveillance guidelines This monitoring will be performed at the investigators site unless otherwise desired by the patient
Endoscopic modalities have been reported to be effective in definitive treatment of early stage esophageal cancer A study comparing endoscopic treatment to surgery in early esophageal cancer using the SEER Surveillance Epidemiology and End Results database showed no difference in the relative hazard of death from esophageal cancer between the two groups The primary endoscopic therapies used in this study were endoscopic mucosal resection EMR and photodynamic therapy PDT Estimated 1 and 3 year survival in this study were 92 and 75 in the endoscopic arm and 92 and 82 in the surgical arm EMR endoscopic excision of superficial cancer has also been shown to be highly effective in mucosal tumors in single center studies Low-risk lesions defined as flat or raised mucosal tumors 2 cm or less that are well-or moderately-differentiated without lymphovascular invasion demonstrate complete response was seen in 966 of patients with 5 year survival of 84 However high-risk lesions defined as greater than 2 cm poorly-differentiated flat-ulcerated or invading into the submucosa have a complete remission rate of only 59
Endoscopic resection is not possible in all mucosal cancers Some cancers are not visible endoscopically but detected only by endoscopic biopsy In other cases the EMR cannot be done due to scarring from previous resection or other therapy especially external beam radiation Management of these cases is problematic PDT using porfimer sodium has been extensively studied for Barretts esophagus with high-grade dysplasia however studies of PDT for early stage esophageal cancer are limited In a recent single site study using PDT and EMR for mucosal cancers overall survival was comparable to a group treated with esophagectomy at the same center with estimated 1 and 3 year survival of 98 and 95 PDT was used in 43 in combination with EMR in the endoscopic treatment group Recurrent carcinoma was detected in 16 of endoscopically treated patients All recurrences were intramucosal cancers with all but one managed by EMR Overall endoscopic treatment was well-tolerated However side effects of PDT are common and include photosensitivity esophageal stricture chest pain nausea vomiting and fever In the US PDT is no longer commonly used in the esophagus due to availability of alternative treatment modalities with less cost and side effects
Endoscopic spray cryotherapy with liquid nitrogen has emerged as an alternative treatment in stage I esophageal cancer in those not suitable for other therapies A recent retrospective review at 10 US centers assessed outcomes in seventy-nine patients Patients included those with esophageal carcinoma who failed refused or were ineligible for conventional therapy including chemotherapy radiation combination chemotherapy and radiation esophagectomy and endoscopic mucosal resection The majority of patients 76 had tumor stage T1N0M0 with mean tumor length of 4 cm All patients were treated with liquid nitrogen spray cryotherapy and forty-nine patients completed treatment Complete response of luminal disease occurred in 612 including 18 of 24 75 with mucosal cancer Follow-up averaged 106 to 115 months and no serious adverse events were reported Longer term follow-up was reported recently in abstract form Complete response was seen in 92 of patients with mucosal cancer with median follow-up of 28 months and overall estimated survival at 1 and 3 years of 98 and 92 respectively
Published studies have demonstrated spray cryotherapy to be safe and well-tolerated with low overall complication rates Tolerance of the procedure is very good All procedures are performed on an outpatient basis Primary side effects include chest pain dysphagia and odynophagia reported in about half of all procedures Mean duration of symptoms was 36 days and many patients had no side effects after treatment Serious adverse events were rare Gastric perforation occurred in one patient with Marfans syndrome Benign esophageal stricture was reported in 13 of patients treated for cancer with previous esophageal narrowing noted in 910 In combination with its relative cost-effectiveness and minimal invasiveness endoscopic spray cryotherapy is an appealing option for those with stage I esophageal cancer who are ineligible or refuse conventional therapies
Study Device truFreezeTM System CSA Medical Inc Baltimore MD
Study Objective The objective of this study is to evaluate the safety and efficacy of endoscopic spray cryotherapy using the CSA Medical Inc truFreeze System for patients with early-stage esophageal cancer T1a N0 M0 who are ineligible or refuse conventional therapy including surgery chemotherapy radiation therapy and endoscopic resection
Study Design Multi-center phase II study
Study Population Patients with early-stage esophageal cancer stage T1aN0M0
Study Duration It is estimated that enrollment will take approximately two years Each subject will remain in the study for up to one-year of treatment and for three years post-treatment It is expected to take five years to collect all required data for this study
Sample size 40
Treatment
Participant receives liquid nitrogen spray cryotherapy every 4 - 8 weeks x no more than 8 cycles Those with complete response to therapy will proceed to surveillance Those with stable or responding disease will continue with cryotherapy Those with progression of disease will discontinue protocol For responding or stable disease after 8 cycles continue treatment beyond 8 cycles until tumor progression or unacceptable toxicity Discontinue protocol therapy for disease progression or unacceptable toxicity
Follow-Up Evaluations and Data Collection
Patients will return for surveillance EGD esophagogastroduodenoscopy procedures with biopsies at 3 6 9 12 18 24 30 and 36 months 4 weeks after the last cryotherapy treatment An estimate of tumor size and response compared to baseline will be made at each endoscopy Biopsies will be performed using large capacity forceps In the area where tumor was present biopsies will be taken every 1 cm in each quadrant Directed biopsies will be performed in any areas that appear suspicious for cancer
CT scan of the chest abdomen and pelvis with oral and intravenous contrast if possible will be performed every 6 months during the follow-up period Full body PETCT may also be performed instead of CT scanning
Endoscopic ultrasound will be performed 6 months after treatment completion to assess for lymphadenopathy
At the conclusion of this protocol regardless of the outcome patients will continue to require periodic surveillance endoscopies for re-emergence of esophageal cancer consistent with the standard surveillance guidelines This monitoring will be performed at the investigators site unless otherwise desired by the patient
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