Clinical trial NCT05774483: Sentinel Node Biopsy Versus Limited Elective Neck Dissection in Early Cancers of Oral Cavity NoDe Negative
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mouth Neoplasms
Keywords: mouth neoplasms
neck dissection
sentinel lymph node biopsy
survival
morbidity
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Tata Memorial Centre
First posted: 2023-03-17
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall survival
timeFrame: 3 years
Secondary outcomes:
measure: Shoulder morbidity
timeFrame: Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment
measure: Neck nodal recurrence
timeFrame: 3 years
measure: Disease free survival
timeFrame: 3 years
measure: Health related Quality of life
timeFrame: Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment
measure: Adverse events related to the surgical procedure and lymphedema
timeFrame: The lymphedema rating will be done at 3 months, at 6 months, 12 months and 24 months of treatment
measure: Cost effectiveness
timeFrame: 3 years
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Navi Mumbai
country: India
facility: ACTREC
state: Maharashtra
city: Varanasi
country: India
facility: Mpmmcc & Hbch
state: Uttar Pradesh
Study officials:
affiliation: Tata Memorial Hospital
name: Richa Vaish, MS, M.Ch
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
citation: 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.