A Trial Evaluating Omission of Radiotherapy to Regional Lymphatic's (Eliminate)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Cisplatin; Radiation: IMRT - adjuvant concurrent CRT/ RT; Radiation: ommission of IMRT - adjuvant concurrent CRT/ RT for regional lymphatics

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.

• Study Type: Interventional
• Enrollment (Estimated): 396
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Aman Sharma, MD; Phone Number: +91117018529339; Email: amans757@gmail.com

Study Locations

• India
  • Haryana
    • Jhajjar, Haryana, India, 124105
      • Recruiting
      • Nci, Aiims
      • Contact: Aman Sharma, MD; Phone Number: +917018529339; Email: amans757@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Aged 18 or above and less than 70 years
2. Stage pT1-4histological confirmed squamous cell carcinoma of oral cavity undergoing radical excision and ipsilateral/bilateral neck dissection.
3. Patient with high risk features: positive or close (≤ 5mm) margin, presence of LVI or PNI, pT3-4
4. At least one dissected hemi-neck (at least 12 nodes recovered in one dissected hemi-neck)
5. Pathological N0/ N1 neck and high risk features undergoing radiotherapy for HNSCC of the oral cavity
6. Brandwein-Gensler (BG) histological risk assessment in all patients
7. Karnofsky performance score greater or equal 70
8. Ability to complete the MD Anderson Dysphagia Inventory (MDADI) and EORTC quality of life questionnaires English or Hindi Version.
9. Timely delivery of PORT preferable within 6weeks of surgery (upto 1-2 weeks of delay beyond 6 weeks is permissible to accommodate for delayed wound healing or other logistics)
10. Written informed consent for treatment.
11. Available to attend long term follow- up

Exclusion Criteria:

1. Non squamous histology
2. Presences of distant metastases
3. pT1-2 disease and no high risk features
4. Pathologically N2/N3 disease.
5. Patients that require re-irradiation for recurrent disease
6. Inadequate neck dissection (less than 12 nodes examined)
7. Primary tumor reaching midline (within 1 cm from midline) and only ipsilateral neck dissection done
8. Initiation of PORT after 8 weeks of radical surgery.
9. Previous radiotherapy to the head and neck region
10. Any invasive malignancy within previous 2 years (other than non melanomatous skin carcinoma or cervical carcinoma in situ).
11. Age < 18 years or > 70 years
12. Brandwein-Gensler (BG) histological risk not done

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Post operative radiotherapy to primary tumor bed and 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.; Radiation: IMRT - adjuvant concurrent CRT/ RT; IMRT - adjuvant concurrent CRT/ RT as 66Gy/33fr or 60Gy/30fr or 50Gy/20fr to primary and regional lymphatics
Experimental: Arm B; Post operative radiotherapy to primary tumor bed but omission of PORT to 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.; Radiation: ommission of IMRT - adjuvant concurrent CRT/ RT for regional lymphatics; IMRT- adjuvant concurrent CRT/ RT as 66Gy/33fr or 60Gy/30fr or 50Gy/20fr / Brachytherapy 40-48 Gy in10-12 fractions twice daily at least 6 hours apart, to primary tumor bed only - elimination of regional lymphatics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional control	Regional control will be assessed as occurrence of any new lesion in the regional /nearby area over time with the help of radiological imaging (CT/MRI/PET-CT) and clinical examination. will be assessed at 3 months, 6 months, 12 months, 18 months, 24 months	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control	Local control will assess the recurrence within the primary tumor site at its original location. Radiographic assessment (CT/MRI/PET-CT) at 3, 6, 12, 18 and 24 months	2 years
Disease free survival	assessed as the length of time that a patient survives without any signs and symptoms of the disease and assessment will be done at every 3, 6, 12, 18, 24 months	2 years
Overall survival	longitudinal assessment every 3, 6, 12, 18, 24 months	2 years
Acute toxicity	Acute toxicity is the side effects that appear within 90 days after the radiation therapy and will be assessed using RTOG acute toxicity scale with grading from 0 to IV where 0 represents no findings and IV being the worst Findings. Higher values wiill be showing worsening of the condition. it will be scored weekly during radiation.	2 years
late toxicity	late toxicity is the side effects that appear after 90 days following the radiation therapy and will be assessed using the Late effects in normal tissues- subjective, objective, management, analytic (LENT SOMA) scale with maximum value of 4 showing very severe / disabling and minimum value of 0 showing no toxicity. Higher values wiill be showing worsening of the condition. longitudinal assessment will be done every 3, 6, 12, 18, 24 months	2 years
Swallowing function	MD Anderson Dysphagia Inventory pre RT, post RT, 3, 6, 12, 18, 24 months	2 years
Quality of life EORTC QLQ C30	EORTC QLQC30 module [longitudinal assessment at 3, 6, 12, 18 and 24 months] The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. High score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	2 years
Quality of life H&N 35	EORTC H&N 35 module [longitudinal assessment at 3, 6, 12, 18 and 24 months] The head & neck cancer module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social eating, social contact and sexuality. There are also eleven single items. For all items and scales (maximum score 100 and minimum score 0), high scores indicate more problems (i.e. there are no function scales in which high scores would mean better functioning). The scoring approach for the QLQ-H&N35 is identical in principle to that for the symptom scales / single items of the QLQ-C30.	2 years

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences
• Collaborators: All India Institute of Medical Sciences, Rishikesh; Jawaharlal Institute of Postgraduate Medical Education & Research; All India Institute of Medical Sciences, Raipur

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): April 3, 2028

Study Registration Dates

• First Submitted: December 6, 2022
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Cisplatin
• Other Study ID Numbers: The Eliminate Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No