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Adjuvant Radiotherapy in Early Stage Oral Cancers (AREST)

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ClinicalTrials.gov Identifier: NCT03853655
Recruitment Status : Recruiting
First Posted : February 25, 2019
Last Update Posted : February 25, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Sudhir Nair, Tata Memorial Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer of Mouth Cancer of the Tongue Cancer of the Head and Neck Buccal Mucosa Cancer Floor of Mouth Carcinoma Radiation: Post-operative adjuvant radiotherapy Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 392 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Radiotherapy in Early Stage Oral Cancers (AREST)
Actual Study Start Date : August 2, 2018
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Oral Cancer

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.





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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


Other Outcome Measures:
  1. 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

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03853655


Contacts
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Contact: Sudhir V Nair, MS, MCh 912224177283 sudhirvr@gmail.com
Contact: Tejpal Gupta, MD 919821548980 tejpalgupta@rediffmail.com

Locations
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India
Dr. B Barooah Cancer Institute Not yet recruiting
Guwahati, Assam, India, 781016
Contact: Ashok Das, MS       akdas171@gmail.com   
HCG Hospital Not yet recruiting
Ahmedabad, Gujarat, India, 380006
Contact: Rajendra Toprani, MCh       rajendratoprani@hotmail.com   
Mazumdar Shaw Medical Centre Not yet recruiting
Bangalore, Karnataka, India, 560100
Contact: Narayana Subramaniam, MS, MCh       narayana.subramaniam@gmail.com   
Principal Investigator: Narayana Subramaniam, MS,MCh         
Sub-Investigator: Naveen H Chandrasekhar, MS,MCh         
Sub-Investigator: Sandeep Jain, MD         
Amrita Institute of Medical Sciences Not yet recruiting
Kochi, Kerala, India, 682041
Contact: Subramania Iyer, MCh       subu.amrita@gmail.com   
Principal Investigator: Subramania Iyer, MS, MCh         
Tata Memorial Centre Recruiting
Mumbai, Maharashtra, India, 400012
Contact: Sudhir V Nair, MBBS, MS    912224177000 ext 7283    sudhirvr@gmail.com   
Contact: Tejpal Gupta, MBBS, MD    919821548980    tejpalgupta@rediffmail.com   
Principal Investigator: Sudhir V Nair, MS,MCh         
Sub-Investigator: Tejpal Gupta, MD         
Sub-Investigator: Sarbani Laskar, MD         
Sub-Investigator: Pankaj Chaturvedi, MS         
Sub-Investigator: Devendra Chaukar, MS         
Sub-Investigator: Anil K D'Cruz, MS,FRCS         
Cancer Institute Adyar Not yet recruiting
Adyar, Tamil Nadu, India, 600020
Contact: Arvind Krishnamurthy, MS, MCh       drarvindkrishnamurthy@gmail.com   
Sponsors and Collaborators
Tata Memorial Hospital
Investigators
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Principal Investigator: Sudhir V Nair, MS, MCh Associate Professor

Additional Information:
Publications:

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Responsible Party: Dr. Sudhir Nair, Associate Professor, Tata Memorial Hospital
ClinicalTrials.gov Identifier: NCT03853655     History of Changes
Other Study ID Numbers: 1713
First Posted: February 25, 2019    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Sudhir Nair, Tata Memorial Hospital:
Cancer of the Mouth
Tongue cancer
Buccal Mucosa cancer
Head and Neck
Oral Cancer
Adjuvant Radiotherapy
Depth of Invasion
Additional relevant MeSH terms:
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Mouth Neoplasms
Head and Neck Neoplasms
Tongue Neoplasms
Neoplasms by Site
Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases