Clinical trial NCT03853655: Adjuvant Radiotherapy in Early Stage Oral Cancers
Official title: Adjuvant Radiotherapy in Early Stage Oral Cancers (AREST)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cancer of Mouth
Cancer of the Tongue
Cancer of the Head and Neck
Buccal Mucosa Cancer
Floor of Mouth Carcinoma
Keywords: Cancer of the Mouth
Tongue cancer
Buccal Mucosa cancer
Head and Neck
Oral Cancer
Adjuvant Radiotherapy
Depth of Invasion
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
Collaborators: name: NATIONAL CANCER GRID
First posted: 2019-02-25
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: loco-regional recurrence free survival
timeFrame: 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 outcomes:
measure: Disease free survival
timeFrame: 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.
measure: Overall survival
timeFrame: Date of randomization to death from any cause or at the end of 36 months after recruitment of the last participant.
Other outcomes:
measure: Quality of life Measurement
timeFrame: at Randomization, 3 months after completion of all treatments, 1 year, 2 years and 3 years after completion of all treatments.
measure: Acute and long-term Radiation toxicity rate
timeFrame: 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.
Locations:
city: Guwahati
country: India
facility: Dr. B Barooah Cancer Institute
state: Assam
city: Ahmedabad
country: India
facility: HCG Hospital
state: Gujarat
city: Goraj
country: India
facility: Kailash Cancer Hospital and Research Centre
state: Gujarat
city: Bangalore
country: India
facility: Sree Sankara Cancer Hospital
state: Karnataka
city: Bangalore
country: India
facility: Mazumdar Shaw Medical Centre
state: Karnataka
city: Kannur
country: India
facility: Malabar Cancer Centre
state: Kerala
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences
state: Kerala
city: Mumbai
country: India
facility: Tata Memorial Centre
state: Maharashtra
Study officials:
affiliation: Associate Professor
name: Sudhir V Nair, MS, MCh
role: PRINCIPAL_INVESTIGATOR
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