Ignite Creation Date:
2024-05-05 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00193765
Status:
UNKNOWN
Last Update Posted:
2017-06-16
First Post:
2005-09-13
Brief Title:
Elective vs Therapeutic Neck Dissection in Treatment of Early Node Negative Squamous Carcinoma of Oral Cavity
Sponsor:
Tata Memorial Hospital
Organization:
Tata Memorial Hospital
Study Overview
Official Title:
Elective Versus Therapeutic Neck Dissection in the Treatment of Early Node Negative Squamous Cell Carcinoma of the Oral Cavity
Status:
UNKNOWN
Status Verified Date:
2017-06
Last Known Status:
ACTIVE_NOT_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:
Cervical nodal metastasis is the single most important prognostic factor in head and neck cancers Appropriate management of the neck is therefore of paramount importance in the treatment of these cancers While it is obvious that the positive neck must be treated controversy has always surrounded the clinically node negative neck with respect to the ideal treatment policyThe situation is difficult with regards to early cancers of the oral cavity T1T2 These cancers are usually treated with surgery where excision is through the per-oral route Elective neck dissection in such a situation is an additional surgical procedure with its associated costs prolonged hospitalization and may be unnecessary in as high as 80 of patients who finally turn out to be pathologically node negative Should the neck be electively treated or there be a wait and watch policy Current practice is that the neck is always addressed whenever there is an increased propensity to cervical metastasis or when patient follow-up is unreliable
There is clearly a need therefore for a large randomized trial that will resolve the issue either way once and for all
Primary Objective
To demonstrate whether elective neck dissection END is equal or superior to the wait and watch policy ie
therapeutic neck dissection TND in the management of the clinically No neck in early T1 T2 cancers of the oral cavity
Secondary Objective
1 Does Ultrasound examination have any role in the routine initial workup of a node negative patient
2 How are patients ideally followed up -does sonography have a role or is clinical examination sufficient
3 Is assessment of tumor thickness by the surgeon at the time of initial surgery accurate -Is there a correlation
4 Identify histological prognostic factors in the primary that may help identify a sub-set of patients at an increased risk for cervical metastasis
There is clearly a need therefore for a large randomized trial that will resolve the issue either way once and for all
Primary Objective
To demonstrate whether elective neck dissection END is equal or superior to the wait and watch policy ie
therapeutic neck dissection TND in the management of the clinically No neck in early T1 T2 cancers of the oral cavity
Secondary Objective
1 Does Ultrasound examination have any role in the routine initial workup of a node negative patient
2 How are patients ideally followed up -does sonography have a role or is clinical examination sufficient
3 Is assessment of tumor thickness by the surgeon at the time of initial surgery accurate -Is there a correlation
4 Identify histological prognostic factors in the primary that may help identify a sub-set of patients at an increased risk for cervical metastasis
Detailed Description:
Stratification criteria
1 Size
2 Sex
3 Site
4 Sonography
Randomization I All patients will be randomly allocated into one of two arms wait and watch policy group or elective neck dissection group Both arms will have similar wide excision of primary tumor in oral cavity per oral route
Randomization II Following surgery and after complete recovery prior to discharge patients will be randomized a second time for follow-up into two arms namely clinical examination versus clinical examination and ultrasonography of neck
SURGICAL PROCEDURE
Primary tumor will be excised after proper exposure via per-oral route
Emphasis will be to achieve a wide clearance with tumor free margins to obviate need of subsequent radiotherapy to primary which would otherwise act as a confounding factor
Neck Patients randomized to neck dissection will undergo a standard supra-omohyoid neck dissection that will involve clearance of nodal Levels I II and IIICompletion MND will be done as and when required Patients who develop metastatic adenopathy on follow-up will undergo a modified neck dissectionradical neck dissection depending on size of metastatic disease Those who have nodes suggestive of metastasis on follow-up sonography will undergo a supraomohyoid dissection frozen section followed by a modified neck dissection if positive
Depth of tumor infiltration though probably most important individual prognostic factor in deciding likelihood of cervical metastasis is unfortunately only available to clinician with final histopathology report Had this parameter been present at time of surgery patient with an increased likelihood of metastasis could have undergone an elective neck dissection while those with a lower incidence could have been saved an unnecessary operation This study would help find out accuracy of correlation between gross assessments of thickness by surgeon on frozen section with final thickness on histopathology and would be of importance in a country like ours where oral cancers are very common and facilities of frozen as well as expertise to measure accurately tumor thickness at histopathology may be unavailable
END POINT OF STUDY
The primary end point will be overall survival and secondary end point will be DFS The patients will be followed up until death or study close whichever is earlier Since overall survival is the primary endpoint patients will be followed up until death telephonic or mail contact is acceptable
Local failures distant metastasis and second primary will be documented
DATA COLLECTION QUALITY CONTROL ANALYSIS
Assuming baseline overall survival of 60 for expected improvement in treatment arm of 10 no of patients required will be is 710 355 in each arm with α005 one sided power of 80 β20 An interim analysis is planned at 250 events death occur
Ultrasound in routine follow-up of all patients will be labor intensive However median follow-up to recurrence in all studies both retrospectiveprospective has been 9 months on an average range 6 months- 13months It will therefore be important to follow patients every vigilantly in first 12 months from primary treatment Follow-up schedules will be First visit 4 weeksFirst 6 months 4-6 weeks 6-12 months 6-8 weeks 12 months- 2 years 8-12 weekly Thereafter 3 monthly
Patients will be encouraged and counseled to come for check up on earlier date within range allowed All patients will be followed up by one of investigators and entry made both in source document as well as central registration cell at CRS with study coordinator At each examination patients will undergo a through head and neck examination as well as an ultrasound if randomized to that arm
SUMMARY OF PROTOCOL AMENDMENTS The first version of the protocol hereafter called Version 1 received approval from the Institutional Ethics Committee in September 2003The most recent version of the protocol hereafter called Version 4 received approval from the Institutional Ethics Committee in June 2014
Version 1 dated September 2003 Version 2 dated December 2008 Version 3 dated August 2011 Version 4 dated June 2014
The number of prospective randomized controlled trials previously reported and reviewed is three in version 1 and the number of prospective Randomized controlled trial previously reported and reviewed has increased to four in version 4 The change was done in version 3
Pre randomization USG findings for lymph nodes were not considered for eligibility criteria Therefore patients with normal indeterminate and those suggestive of metastasis were eligible for trial inclusion in version 1 and Patients with pre randomization ultrasound neck findings suggestive of metastasis were excluded in version 4 The change was done in version 2
Based on pre-randomization ultrasound neck findings patients were stratified between those with normal versus indeterminate versus suspicious for metastasis in version 1 and Patients stratification was between normal versus indeterminate ultrasound findings in version 4 The change was done in version 2
Patients and investigators blinded to pre- randomization ultrasound neck findings in version 1 and Patients and investigators are no longer blinded to pre- randomization ultrasound neck findings in version4 The change was done in Version 2
The end points are locoregional recurrence survival in version 1 and The secondary endpoint of the study has been explicitly clarified to be disease-free survival in version 4 The change was done in Version 3
Nodal relapse and Regional Recurrence have been defined explicitly in version 4 The change was done in version 3
Ethical Concerns
Protocol amendment details
Protocol amendment was accepted by scientific ethics committeeInstititional Review board on 29122008 as follows
All patients will undergo a pre randomization ultrasonography of neck If USG report suggests metastasis patients would be treated according to merit to avoid ethical concerns and if USG report is normal or indeterminate patients would be randomized for trial This protocol amendment is done in view of following 2 reasons
Very often patients are uncomfortable to give consent when they are explained that initial ultrasonography report will be blinded and findings will not be considered in deciding patients treatment plan This resulted in lower recruitment of patients and it also raised ethical issues when blind was not adequately maintained especially if sonography suggested metastasis
To overcome a difference of opinion amongst examining clinicians about a clinically significant node
However breaking blind would have no bearing on outcome impact of this study
1 Size
2 Sex
3 Site
4 Sonography
Randomization I All patients will be randomly allocated into one of two arms wait and watch policy group or elective neck dissection group Both arms will have similar wide excision of primary tumor in oral cavity per oral route
Randomization II Following surgery and after complete recovery prior to discharge patients will be randomized a second time for follow-up into two arms namely clinical examination versus clinical examination and ultrasonography of neck
SURGICAL PROCEDURE
Primary tumor will be excised after proper exposure via per-oral route
Emphasis will be to achieve a wide clearance with tumor free margins to obviate need of subsequent radiotherapy to primary which would otherwise act as a confounding factor
Neck Patients randomized to neck dissection will undergo a standard supra-omohyoid neck dissection that will involve clearance of nodal Levels I II and IIICompletion MND will be done as and when required Patients who develop metastatic adenopathy on follow-up will undergo a modified neck dissectionradical neck dissection depending on size of metastatic disease Those who have nodes suggestive of metastasis on follow-up sonography will undergo a supraomohyoid dissection frozen section followed by a modified neck dissection if positive
Depth of tumor infiltration though probably most important individual prognostic factor in deciding likelihood of cervical metastasis is unfortunately only available to clinician with final histopathology report Had this parameter been present at time of surgery patient with an increased likelihood of metastasis could have undergone an elective neck dissection while those with a lower incidence could have been saved an unnecessary operation This study would help find out accuracy of correlation between gross assessments of thickness by surgeon on frozen section with final thickness on histopathology and would be of importance in a country like ours where oral cancers are very common and facilities of frozen as well as expertise to measure accurately tumor thickness at histopathology may be unavailable
END POINT OF STUDY
The primary end point will be overall survival and secondary end point will be DFS The patients will be followed up until death or study close whichever is earlier Since overall survival is the primary endpoint patients will be followed up until death telephonic or mail contact is acceptable
Local failures distant metastasis and second primary will be documented
DATA COLLECTION QUALITY CONTROL ANALYSIS
Assuming baseline overall survival of 60 for expected improvement in treatment arm of 10 no of patients required will be is 710 355 in each arm with α005 one sided power of 80 β20 An interim analysis is planned at 250 events death occur
Ultrasound in routine follow-up of all patients will be labor intensive However median follow-up to recurrence in all studies both retrospectiveprospective has been 9 months on an average range 6 months- 13months It will therefore be important to follow patients every vigilantly in first 12 months from primary treatment Follow-up schedules will be First visit 4 weeksFirst 6 months 4-6 weeks 6-12 months 6-8 weeks 12 months- 2 years 8-12 weekly Thereafter 3 monthly
Patients will be encouraged and counseled to come for check up on earlier date within range allowed All patients will be followed up by one of investigators and entry made both in source document as well as central registration cell at CRS with study coordinator At each examination patients will undergo a through head and neck examination as well as an ultrasound if randomized to that arm
SUMMARY OF PROTOCOL AMENDMENTS The first version of the protocol hereafter called Version 1 received approval from the Institutional Ethics Committee in September 2003The most recent version of the protocol hereafter called Version 4 received approval from the Institutional Ethics Committee in June 2014
Version 1 dated September 2003 Version 2 dated December 2008 Version 3 dated August 2011 Version 4 dated June 2014
The number of prospective randomized controlled trials previously reported and reviewed is three in version 1 and the number of prospective Randomized controlled trial previously reported and reviewed has increased to four in version 4 The change was done in version 3
Pre randomization USG findings for lymph nodes were not considered for eligibility criteria Therefore patients with normal indeterminate and those suggestive of metastasis were eligible for trial inclusion in version 1 and Patients with pre randomization ultrasound neck findings suggestive of metastasis were excluded in version 4 The change was done in version 2
Based on pre-randomization ultrasound neck findings patients were stratified between those with normal versus indeterminate versus suspicious for metastasis in version 1 and Patients stratification was between normal versus indeterminate ultrasound findings in version 4 The change was done in version 2
Patients and investigators blinded to pre- randomization ultrasound neck findings in version 1 and Patients and investigators are no longer blinded to pre- randomization ultrasound neck findings in version4 The change was done in Version 2
The end points are locoregional recurrence survival in version 1 and The secondary endpoint of the study has been explicitly clarified to be disease-free survival in version 4 The change was done in Version 3
Nodal relapse and Regional Recurrence have been defined explicitly in version 4 The change was done in version 3
Ethical Concerns
Protocol amendment details
Protocol amendment was accepted by scientific ethics committeeInstititional Review board on 29122008 as follows
All patients will undergo a pre randomization ultrasonography of neck If USG report suggests metastasis patients would be treated according to merit to avoid ethical concerns and if USG report is normal or indeterminate patients would be randomized for trial This protocol amendment is done in view of following 2 reasons
Very often patients are uncomfortable to give consent when they are explained that initial ultrasonography report will be blinded and findings will not be considered in deciding patients treatment plan This resulted in lower recruitment of patients and it also raised ethical issues when blind was not adequately maintained especially if sonography suggested metastasis
To overcome a difference of opinion amongst examining clinicians about a clinically significant node
However breaking blind would have no bearing on outcome impact of this study
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