Sentinel Node Biopsy Versus Limited Elective Neck Dissection in Early Cancers of Oral Cavity NoDe Negative (SECOND N0)

July 14, 2025 updated by: Richa Vaish, Tata Memorial Hospital

Sentinel Node Biopsy Versus Limited Elective Neck Dissection in Early Cancers of Oral Cavity NoDe Negative (SECOND N0): Non-inferiority Phase III Trial

The goal of this clinical trial is to compare the survival outcomes, morbidity and cost-effectiveness of sentinel node biopsy versus limited elective neck dissection in node-negative early oral cancers.

The main questions it aims to answer are:

  • Survival outcomes
  • Morbidity outcomes
  • Cost-effectiveness

Participants will either undergo sentinel node biopsy followed by completion neck dissection if sentinel node is reported to be metastatic (SNB) or limited elective neck dissection where level IIb will be cleared only if level IIa is metastatic (limited END). The study will compare the outcomes in the two cohorts.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Based on the current literature, we know that elective neck dissection (END) is mandatory in clinically node-negative early oral cancers. However, this leads to overtreatment and morbidity in about 55-80% of patients. The emergence of recent level I evidence makes SNB the standard of care in this setting. However, its limitation of being a two-staged procedure, steep learning curve, the burden on resources, lack of infrastructure, short-lasting decrease in morbidity and lack of cost-effectiveness data limits its wide applicability. It is our routine departmental practice of performing limited neck dissection clearing level I-III/IV sparing level IIb which is cleared only if level IIa is metastatic. It is hypothesized that limited END would limit the morbidity of shoulder dysfunction and be a more feasible and cost-effective treatment option which could be a suitable alternative to SNB in this setting without compromising the survival outcomes. With this background, we propose to embark upon a phase III RCT comparing the oncologic outcomes and morbidity of SNB versus limited END. We hypothesize that limited END would have survival outcomes non-inferior, morbidity similar to SNB with higher cost-effectiveness.

Aims and objectives:

Aim To compare the survival outcomes, morbidity and cost-effectiveness of SNB versus limited END in node-negative early oral cancers

Primary objective

1) Overall survival

Secondary objectives

  1. Shoulder morbidity (key secondary endpoint) longitudinally up to 2 years
  2. Disease-free survival
  3. Neck nodal recurrence-free survival
  4. Other side effects (chyle leak, hematoma, lymphoedema)
  5. Longitudinal Quality of life up to 2 years
  6. Cost-effective analysis

Exploratory objectives Blood and tumour tissue will be collected and banked for biomarker studies. Exploratory analyses will be conducted at a later date. Efforts may be directed to identify the biomarkers to predict nodal metastasis.

Study Type

Interventional

Enrollment (Estimated)

508

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • India
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Recruiting
        • Tata Memorial Hospital
        • Contact:
      • Navi Mumbai, Maharashtra, India
        • Not yet recruiting
        • ACTREC
        • Contact:
    • Uttar Pradesh
      • Varanasi, Uttar Pradesh, India
        • Not yet recruiting
        • Mpmmcc & Hbch
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age >18 years of age
  2. Biopsy-proven invasive squamous cell carcinoma involving the site tongue and buccal mucosa
  3. T1 and T2 lesions as per AJCC TNM 8 edition
  4. Clinicoradiologically node negative
  5. Amenable to per oral excision
  6. Treatment naïve
  7. No other site of malignancy

Exclusion Criteria:

  1. Previous surgery in the head and neck region,
  2. Upper alveolar or palatal lesions
  3. Large heterogeneous leukoplakia or other premalignant lesions
  4. Previous malignancy in the head and neck region
  5. Patients requiring the free flap reconstruction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sentinel node biopsy
Procedure: Sentinel Node Biopsy
The Sentinel node will be localized after injecting peritumoral nano colloid followed by dynamic lymphoscintigraphy and SPECT localization. Methylene blue or indocyanine green may be used but not mandatory as an adjunct for lymphoscintigraphy for node localization. Intraoperatively the node will be identified using a hand-held gamma probe. The sentinel node will be processed on a frozen section, histopathological processing with serial step sectioning, and immunohistochemistry. If reported as metastatic, then a single-stage or second-stage completion neck dissection will be performed.
Experimental: Limited elective neck dissection
Procedure: Limited Elective Neck Dissection
Patients who are allocated to the limited END arm will undergo dissection of level I, IIa and III/IV nodes sparing level IIb. Level IIa will be subjected to a frozen section and if reported as metastatic will mandate clearance of level IIb.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 3 years
Defined from the date of randomization to death due to any cause
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Shoulder morbidity
Time Frame: Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment
It will be assessed using the neck dissection impairment index (NDII). The range of movement of the shoulder will also be assessed using a goniometer
Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment
Neck nodal recurrence
Time Frame: 3 years
Defined from the date of randomization to isolated neck node recurrence or death due to any cause
3 years
Disease free survival
Time Frame: 3 years
Defined from the date of randomization to any recurrence (local, regional or distant metastasis) and second primary in the oral cavity
3 years
Health related Quality of life
Time Frame: Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment
Quality of life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 and QLQ HN35 instruments
Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment
Adverse events related to the surgical procedure and lymphedema
Time Frame: The lymphedema rating will be done at 3 months, at 6 months, 12 months and 24 months of treatment
Details of the intra and perioperative delay including injury to critical structures, chyle leak, haemorrhage, and head and neck lymphedema
The lymphedema rating will be done at 3 months, at 6 months, 12 months and 24 months of treatment
Cost effectiveness
Time Frame: 3 years
Based on direct cost comparison
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Hospital

Collaborators

Tata Memorial Centre

Investigators

  • Principal Investigator: Richa Vaish, MS, M.Ch, Tata Memorial Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 16, 2025

Primary Completion (Estimated)

April 1, 2032

Study Completion (Estimated)

April 1, 2034

Study Registration Dates

First Submitted

March 7, 2023

First Submitted That Met QC Criteria

March 7, 2023

First Posted (Actual)

March 17, 2023

Study Record Updates

Last Update Posted (Actual)

July 17, 2025

Last Update Submitted That Met QC Criteria

July 14, 2025

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4081

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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