NCT07528495

A Trial Evaluating Omission of Radiotherapy to Regional Lymphatic's

The Eliminate Trial: A Phase II/III Randomised Trial Evaluating Omission of Radiotherapy to Regional Lymphatic's in pN0/N1 Neck for Oral Cavity Carcinomas

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 396 (estimated)
• Sponsor: All India Institute of Medical Sciences · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

The present study is a phase II/III prospective randomized trial designed to determine whether eliminating of post operative radiotherapy to regional lymphatics in pN0-N1oral cavity is associated with similar treatment outcomes.

Detailed description

Patients of oral cavity squamous cell carcinoma (OCSCC) undergoing surgery are at risk of local as well as regional failure. Postoperative radiotherapy (PORT) is often added to radical surgery with intent to reduce loco regional recurrence and improve overall survival in patients with high-risk features. High risk feature include patients with extra capsular extension, positive/ close margins, more than one lymph node involved, pT3 or pT4 primary disease, lymphovascular invasion (LVI), perineural invasion (PNI). PORT alone or in combination with concurrent chemotherapy is associated with reductions in loco regional recurrence as well as improvement in overall survival (OS). Benefits associated with PORT often come at the expense of development of significant acute and late morbidities that include dysphagia, mucositis, xerostomia, dermatitis, ototoxicity, fibrosis, dental caries, osteoradionecrosis, change in voice changes, and hypothyroidism. Radiotherapy (RT) portals for head and neck squamous cell carcinomas (HNSCC) have traditionally included primary disease plus treatment of bilateral neck. Larger RT treatment volumes generally correlate with increased incidence of radiation induced morbidity .There is potential to reduce radiation morbidity if RT portals can be reduced without compromising treatment outcomes. One such situation is pN0-pN1neck status. However, at present there is no definite consensus as regards to omission of PORT to regional lymphatic's in pN0 -pN1neck and the benefit of omission of PORT largely remains unknown. In a non randomized prospective phase II trial, that eliminated PORT to pN0 necks for patients with locally advanced HNSCC, showed that omitting PORT resulted in excellent control rates in the unirradiated neck. This study included 19% patients with OCSCC. Several retrospective series for OCSCC have reported that RT to tumor bed alone in N0-1 neck is associated with similar treatment outcomes as compared to RT to loco-regional sites.The ongoing PRESERVE study is addressing this question and will generate high level evidence in terms of oncologic outcomes, quality of life and toxicity.The PRESERVE study is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). The Eliminate trial is similar to the PRESERVE study but will exclude patients with PN2-pN3 disease. Unlike the PRESERVE study, the ongoing trial will also consider omission PORT in patients with pN1 disease. A risk of nodal recurrence of 15%-20% has traditionally an indication warrant radiation to a nodal basin. Involvement of two or more nodes is a definite indication for PORT. However, in patients in whom the metastases are limited to a single, ipsilateral positive lymph node not larger than 3 cm (ie, N1), and the routine use of PORT is controversial. In such situations PORT delivery is at discretion of the treating physician. This discrepancy (pN1 status) was also seen in EORTC trial 22931 and RTOG trial 9501criteria for definition of high risk disease. In the EORTC trial 43% of patients enrolled in the trial hadpN0-1 status whereas only 6% of the patients enrolled in the RTOG trial hadpN0-1. The RTOG used the criteria of two or more lymph nodes as indication of PORT whereas in the EORTC trial stage III -IV were one of the criteria for delivery of PORT. There is no prospective study that has considered omission of PORT in pN1OCSCC. Large retrospective series have demonstrated the benefit of PORT for pN1 disease yet there is declining uses of PORT for pN1 OSCC .The ASCO guidelines also do not recommend PORT in pN1 after adequate neck dissection. A recently published study of the National Cancer Database that comprised 1909 OSCC patients with pN1 disease showed a statistically significant survival benefit in favour of PORT (adjusted HR 0.82). The study reported similar benefit in patients with inadequate and adequate neck dissections. In light of this background, the Eliminate trial is designed to test omission of regional RT in pN0-1 neck. The aim of this study is evaluate feasibility of omission of RT to regional lymphatics in pN0/pN1 patients undergoing radical surgery with adequate lymph node dissection for oral cavity HNSCC.

Conditions

• Head and Neck Cancer

Interventions

Type	Name	Description
RADIATION	IMRT - adjuvant concurrent CRT/ RT	IMRT - adjuvant concurrent CRT/ RT as 66Gy/60 Gy in 33/30 fractions to primary and regional lymphatics
RADIATION	ommission of IMRT - adjuvant concurrent CRT/ RT for regional lymphatics	IMRT- adjuvant concurrent CRT/ RT as 66Gy/60 Gy in 33/30 fractions/ Brachytherapy 40-48 Gy in10-12 fractions twice daily at least 6 hours apart, to primary tumor bed only \- elimination of regional lymphatics
DRUG	Cisplatin	Cisplatin is a antineoplastic drug, will be given during the radiation at a dose of 40 mg/m2 weekly to a cumulative dose of at least 200 mg/m2 in case of margin positive disease.

Timeline

• Start date: 2024-04-03
• Primary completion: 2027-12-30
• Completion: 2028-04-03
• First posted: 2026-04-14
• Last updated: 2026-04-14

Locations

1 site across 1 country: India