Elective vs Therapeutic Neck Dissection in Treatment of Early Node Negative Squamous Carcinoma of Oral Cavity
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|ClinicalTrials.gov Identifier: NCT00193765|
Recruitment Status : Unknown
Verified June 2017 by A K D'Cruz, Tata Memorial Hospital.
Recruitment status was: Active, not recruiting
First Posted : September 19, 2005
Last Update Posted : June 16, 2017
|First Submitted Date ICMJE||September 13, 2005|
|First Posted Date ICMJE||September 19, 2005|
|Last Update Posted Date||June 16, 2017|
|Study Start Date ICMJE||January 2004|
|Estimated Primary Completion Date||June 2019 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Overall Survival [ Time Frame: 5 years ]
survival would be calculated as time period between date of randomization and date of death from any cause or last follow up
|Original Primary Outcome Measures ICMJE
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Elective vs Therapeutic Neck Dissection in Treatment of Early Node Negative Squamous Carcinoma of Oral Cavity|
|Official Title ICMJE||Elective Versus Therapeutic Neck Dissection in the Treatment of Early Node Negative Squamous Cell Carcinoma of the Oral Cavity|
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 policy.The situation is difficult with regards to early cancers of the oral cavity (T1/T2). 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.
To demonstrate whether elective neck dissection (END) is equal or superior to the wait and watch policy i.e.
therapeutic neck dissection (TND) in the management of the clinically No neck in early T1 /T2 cancers of the oral cavity.
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.
Primary: tumor will be excised after proper exposure via per-oral route.
Neck: Patients randomized to neck dissection will undergo a standard supra-omohyoid neck dissection that will involve clearance of nodal Levels I, II, and III.Completion MND will be done as and when required. Patients who develop metastatic adenopathy on follow-up will undergo a modified neck dissection/radical 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 α=0.05 (one sided) & power of 80% (β=20). 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 retrospective/prospective 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 weeks;First 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 2003.The 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.
Protocol amendment details:
Protocol amendment was accepted by scientific ethics committee/Instititional Review board on 29/12/2008 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 patient's 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 Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Oral Cancer|
|Study Arms ICMJE||
|Publications *||D'Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, Agarwal JP, Pantvaidya G, Chaukar D, Deshmukh A, Kane S, Arya S, Ghosh-Laskar S, Chaturvedi P, Pai P, Nair S, Nair D, Badwe R; Head and Neck Disease Management Group. Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. N Engl J Med. 2015 Aug 6;373(6):521-9. doi: 10.1056/NEJMoa1506007. Epub 2015 May 31.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||June 2019|
|Estimated Primary Completion Date||June 2019 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 75 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||India|
|Removed Location Countries|
|NCT Number ICMJE||NCT00193765|
|Other Study ID Numbers ICMJE||TMH/131/2003|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||
|Responsible Party||A K D'Cruz, Tata Memorial Hospital|
|Study Sponsor ICMJE||Tata Memorial Hospital|
|Collaborators ICMJE||Not Provided|
|PRS Account||Tata Memorial Hospital|
|Verification Date||June 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP