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

NCT ID: NCT05774483

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 508 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-16
• Study Completion Date: 2034-04-30

Brief Summary

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.

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.

Conditions

Mouth Neoplasms; Oral Cancers; Oral Squamous Cell Carcinoma (OSCC); Oral Squamous Cell Carcinomas; Sentinel Lymph Node Biopsy; Sentinel Lymph Node Biopsy (SLNB); Sentinel Lymph Node

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sentinel node biopsy

Group Type: ACTIVE_COMPARATOR

Sentinel Node Biopsy

Intervention Type: PROCEDURE

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.

Limited elective neck dissection

Group Type: EXPERIMENTAL

Limited Elective Neck Dissection

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tata Memorial Centre

OTHER

Sponsor Role: collaborator

Tata Memorial Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Richa Vaish

Professor and Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richa Vaish, MS, M.Ch

Role: PRINCIPAL_INVESTIGATOR

Tata Memorial Hospital

Locations

Tata Memorial Hospital

Mumbai, Maharashtra, India

Site Status: RECRUITING

ACTREC

Navi Mumbai, Maharashtra, India

Site Status: NOT_YET_RECRUITING

Mpmmcc & Hbch

Varanasi, Uttar Pradesh, India

Site Status: NOT_YET_RECRUITING

Countries

India

Central Contacts

Richa Vaish, MS, M.Ch

Role: CONTACT

drvaishricha@gmail.com

02224177000 ext. 7238

Facility Contacts

Richa Vaish, MS, M.Ch

Role: primary

drvaishricha@gmail.com

022-24177000 ext. 7238

Richa Vaish, MS, M.Ch

Role: primary

drvaishricha@gmail.com

022-24177000

Aseem Mishra, MS, M.Ch

Role: primary

draseemmishra@gmail.com

0542-6917700

References

Garrel R, Poissonnet G, Moya Plana A, Fakhry N, Dolivet G, Lallemant B, Sarini J, Vergez S, Guelfucci B, Choussy O, Bastit V, Richard F, Costes V, Landais P, Perriard F, Daures JP, de Verbizier D, Favier V, de Boutray M. Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1-T2N0 Oral and Oropharyngeal Cancer. J Clin Oncol. 2020 Dec 1;38(34):4010-4018. doi: 10.1200/JCO.20.01661. Epub 2020 Oct 14.

Reference Type: BACKGROUND

PMID: 33052754 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26027881 (View on PubMed)

Hutchison IL, Ridout F, Cheung SMY, Shah N, Hardee P, Surwald C, Thiruchelvam J, Cheng L, Mellor TK, Brennan PA, Baldwin AJ, Shaw RJ, Halfpenny W, Danford M, Whitley S, Smith G, Bailey MW, Woodwards B, Patel M, McManners J, Chan CH, Burns A, Praveen P, Camilleri AC, Avery C, Putnam G, Jones K, Webster K, Smith WP, Edge C, McVicar I, Grew N, Hislop S, Kalavrezos N, Martin IC, Hackshaw A. Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort. Br J Cancer. 2019 Nov;121(10):827-836. doi: 10.1038/s41416-019-0587-2. Epub 2019 Oct 15.

Reference Type: BACKGROUND

PMID: 31611612 (View on PubMed)

Dhar H, Vaish R, D'Cruz AK. Comment on "Nationwide randomised trial evaluating elective neck dissection for early-stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort.". Br J Cancer. 2020 Sep;123(7):1198-1199. doi: 10.1038/s41416-020-0981-9. Epub 2020 Jul 16. No abstract available.

Reference Type: BACKGROUND

PMID: 32669674 (View on PubMed)

Vaish R, Hawaldar R, Gupta S, Dandekar M, Shah S, Chaukar D, Pantvaidya G, Deshmukh A, Chaturvedi P, Pai P, Nair D, Nair S, Thakur M, Ghosh-Laskar S, Agarwal JP, D'Cruz AK. N0 neck trial: Does intensification of follow-up (Ultrasound + Physical Examination) influence outcomes in early-stage oral cancer? Eur J Cancer. 2024 Jun;204:114064. doi: 10.1016/j.ejca.2024.114064. Epub 2024 Apr 16.

Reference Type: BACKGROUND

PMID: 38705028 (View on PubMed)

Other Identifiers

4081

Identifier Type: -

Identifier Source: org_study_id