Adjuvant Radiotherapy in Early Stage Oral Cancers (AREST)

April 21, 2024 updated by: Dr. Sudhir Nair, Tata Memorial Hospital

Adjuvant Radiotherapy in Early Stage Oral Cancers (AREST)

This study will assess the benefit of postoperative adjuvant radiotherapy in patients with an early oral squamous cell carcinoma (OSCC) having tumor thickness more than or equal to 5mm. The study population will consist of patients who have been treated by surgery for early stage oral tongue cancers. Patients with a close or positive margin (</= 5mm) and or with metastatic neck node(s) will be excluded. Selected patients will be randomized into two groups. The group I will be observed after surgery and group II will receive adjuvant radiotherapy as per protocol.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The aim of this study is to assess the benefit of postoperative adjuvant radiotherapy in patients with an early oral squamous cell carcinoma (OSCC) having a tumor depth of invasion more than or equal to 5mm.

Primary objective:

To determine the impact of postoperative adjuvant radiotherapy on locoregional recurrence-free survival in patients with early-stage oral tongue cancer with tumor thickness ≥ 5 mm.

Secondary objectives:

  1. To compare disease-free survival and overall survival between the two groups.
  2. To assess and compare the quality of life changes between the two groups.
  3. To assess the acute and long-term radiation toxicity.

We will be conducting a Phase III Open-Label Prospective Randomized Controlled Trial using stratified randomization. Patients will be randomized into two groups:

Group I: Control arm (Observation only) Group II: Study arm (Postoperative adjuvant radiotherapy)

Patients will be stratified on the following factors

  1. Presence of Perineural Invasion (PNI)/Lympho-Vascular Emboli (LVE)
  2. Histological grade (well-differentiated/moderately differentiated vs poorly differentiated)
  3. Tongue/Floor of Mouth vs Buccal Mucosa.

Study procedures:

The study population will consist of patients who have been treated by surgery for early-stage oral cancers. Patients satisfying the inclusion-exclusion criteria will be included in the study after obtaining a valid, written and informed consent. The depth of invasion will be assessed microscopically by measuring the maximum vertical bulk of the tumor from the normal mucosal surface to the deepest point of invasion. After reviewing the histopathological report, patients will be randomized to one of the 2 arms. Patients belonging to study arm (Group II) will receive adjuvant radiotherapy 60 Gray, 30 fractions for 30 days over 6 weeks as routinely prescribed at Tata Memorial Center (TMC) and will receive the treatment within or by 6 weeks after surgery.

Both the groups (Group I and Group II) will be under regular follow-up with 3 monthly intervals for the first 2 years and 6 monthly for the next 3 years and once a year thereafter. At each follow-up, patients will be evaluated clinically for evidence of locoregional tumor recurrence. The locoregional recurrence-free survival will be calculated based on the difference between the date of randomization and the date of biopsy-proven recurrence. We will also record the overall survival in both groups. The quality of life will be assessed at each follow-up regular intervals using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ H&N-35 ) and EORTC QLQ-C 30. The radiation toxicity will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Study Type

Interventional

Enrollment (Actual)

392

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Assam
      • Guwahati, Assam, India, 781016
        • Dr. B Barooah Cancer Institute
    • Gujarat
      • Ahmedabad, Gujarat, India, 380006
        • HCG Hospital
      • Goraj, Gujarat, India, 391760
        • Kailash Cancer Hospital and Research Centre
    • Karnataka
      • Bangalore, Karnataka, India, 560004
        • Sree Sankara Cancer Hospital
      • Bangalore, Karnataka, India, 560100
        • Mazumdar Shaw Medical Centre
    • Kerala
      • Kannur, Kerala, India, 670103
        • Malabar Cancer Centre
      • Kochi, Kerala, India, 682041
        • Amrita Institute of Medical Sciences
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Tata Memorial Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Post-operative early stage squamous cell carcinoma of the oral cavity (Oral Tongue, Buccal Mucosa, Floor of mouth). (pT1, pT2, N0 as defined in the AJCC Classification 8th edition.
  2. Adequate surgery (Defined as wide local excision of the primary tumor with tumor-free margin ≥ 5mm and ipsilateral selective neck dissection addressing levels I-III at minimum.)
  3. Written informed consent.
  4. Age ≥18 years
  5. Eastern Co-operative Oncology Group (ECOG) Performance Status 0-2
  6. The depth of invasion (DOI) ≥ 5 mm.
  7. Compliance to therapy and follow-up
  8. The interval from surgery to adjuvant radiotherapy ≤ 6 weeks

Exclusion Criteria:

  1. pT3/pT4 (as specified in the AJCC 8th edition).
  2. Depth of invasion < 5mm.
  3. Any neck nodal metastasis with or without extra nodal extension
  4. Tumor-free margin < 5 mm
  5. Non-squamous histology
  6. Pregnant woman
  7. Prior h/o any other malignancy in the last five years
  8. Prior therapeutic irradiation of the head and neck.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control arm
Patients in this arm will be observed and kept under active follow-up after surgery for the primary.
Experimental: Study arm
Intervention in the study arm will be in the form of post-operative adjuvant radiotherapy starting within 6-weeks after primary surgery.
Radiation: Post-operative adjuvant radiotherapy

Conventional treatment planning, as well as intensity-modulated radiation therapy (IMRT) planning, would be allowed on the study with patients being stratified on the RT technique.

Treatment would be delivered on telecobalt unit (gamma-rays/linear accelerator (6MV photons). All fields would be treated daily.

Phase I: 46 Gray(Gy) in 23 fractions over 4.5 weeks Phase II: 14Gray in 7 fractions over 1.5 weeks

For IMRT, inverse planning would be done on a commercial TPS configured to deliver IMRT using 6MV photons. Patients shall be treated using the simultaneous integrated boost (SIB) technique with 5 fractions being delivered every week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
loco-regional recurrence free survival
Time Frame: Date of randomization to loco regional recurrence (date of proven biopsy date) or at the end of 36 months after recruitment of the last participant.
Measures the number of local or regional recurrences in both arm over a defined time frame.
Date of randomization to loco regional recurrence (date of proven biopsy date) or at the end of 36 months after recruitment of the last participant.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival
Time Frame: Calculated as difference of date of randomization to date of first documented recurrence or relapse, second primary or death or at the end of 36 months after recruitment of the last participant.
time from the beginning of an intervention until patient experiences a recurrence, a new primary cancer or death.
Calculated as difference of date of randomization to date of first documented recurrence or relapse, second primary or death or at the end of 36 months after recruitment of the last participant.
Overall survival
Time Frame: Date of randomization to death from any cause or at the end of 36 months after recruitment of the last participant.
Date of Randomization to death from any cause
Date of randomization to death from any cause or at the end of 36 months after recruitment of the last participant.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life Measurement
Time Frame: at Randomization, 3 months after completion of all treatments, 1 year, 2 years and 3 years after completion of all treatments.
Measured using EORTC QLQ H&N-35 and EORTC QLQ-C 30
at Randomization, 3 months after completion of all treatments, 1 year, 2 years and 3 years after completion of all treatments.
Acute and long-term Radiation toxicity rate
Time Frame: From the date of randomization until the date of first documented disease recurrence or date of death from any cause, assessed up to 36 months.
The Common Terminology Criteria for Adverse Events (CTCAE V 4.0) will be used for assessing the Adverse events. The Radiation Therapy Oncology Group (RTOG) acute and late radiation morbidity scoring criteria will be used for assessing the radiotherapy related toxicity.
From the date of randomization until the date of first documented disease recurrence or date of death from any cause, assessed up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Hospital

Collaborators

NATIONAL CANCER GRID

Investigators

  • Principal Investigator: Sudhir V Nair, MS, MCh, Associate Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2018

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

June 20, 2017

First Submitted That Met QC Criteria

February 22, 2019

First Posted (Actual)

February 25, 2019

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 21, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1713

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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