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

Mouth Neoplasms Clinical Trial

— SECOND N0  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05774483
• Other study ID #: 4081
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2023
• Est. completion date: April 2034

Study information

• Verified date: March 2023
• Source: Tata Memorial Hospital
• Contact: Richa Vaish, MS, M.Ch
• Phone: 02224177000
• Email: drvaishricha[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 508
• Est. completion date: April 2034
• Est. primary completion date: April 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Mouth Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
India	Tata Memorial Centre	Mumbai	Maharashtra

Sponsors (2)

Lead Sponsor	Collaborator
Tata Memorial Hospital	Tata Memorial Centre

Country where clinical trial is conducted

India, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

Hasegawa Y, Tsukahara K, Yoshimoto S, Miura K, Yokoyama J, Hirano S, Uemura H, Sugasawa M, Yoshizaki T, Homma A, Chikamatsu K, Suzuki M, Shiotani A, Matsuzuka T, Kohno N, Miyazaki M, Oze I, Matsuo K, Kosuda S, Yatabe Y; HNCMM Research Group. Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial. J Clin Oncol. 2021 Jun 20;39(18):2025-2036. doi: 10.1200/JCO.20.03637. Epub 2021 Apr 20. — View Citation

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. Erratum In: Br J Cancer. 2022 Mar;126(5):831. — View Citation

Vaish R, Gupta S, D'Cruz AK. Elective versus Therapeutic Neck Dissection in Oral Cancer. N Engl J Med. 2015 Dec 17;373(25):2477. doi: 10.1056/NEJMc1511351. No abstract available. — View Citation

Vaish R, Mittal N, Mahajan A, Rane SU, Agrawal A, D'Cruz AK. Sentinel node biopsy in node negative early oral cancers: Solution to the conundrum! Oral Oncol. 2022 Nov;134:106070. doi: 10.1016/j.oraloncology.2022.106070. Epub 2022 Aug 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Defined from the date of randomization to death due to any cause	3 years
Secondary	Shoulder morbidity	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
Secondary	Neck nodal recurrence	Defined from the date of randomization to isolated neck node recurrence or death due to any cause	3 years
Secondary	Disease free survival	Defined from the date of randomization to any recurrence (local, regional or distant metastasis) and second primary in the oral cavity	3 years
Secondary	Health related Quality of life	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
Secondary	Adverse events related to the surgical procedure and lymphedema	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
Secondary	Cost effectiveness	Based on direct cost comparison	3 years