Adjuvant Radiotherapy in Early Stage Oral Cancers

Not Applicable

Active, not recruiting

• Conditions: Buccal Mucosa Cancer; Floor of Mouth Carcinoma; Cancer of Mouth; Cancer of the Tongue; Cancer of the Head and Neck
• Interventions: Radiation: Post-operative adjuvant radiotherapy

• Registration Number: NCT03853655
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2017-06-20
• Study Start: 2018-08-02
• Study First Submitted QC: 2019-02-22
• Study First Posted: 2019-02-25
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-21
• Last Update Posted: 2024-04-23
• Primary Completion: 2026-08-01
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 392

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study arm	Post-operative adjuvant radiotherapy	Intervention in the study arm will be in the form of post-operative adjuvant radiotherapy starting within 6-weeks after primary surgery.

Primary Outcome Measures

Name	Time	Method
loco-regional recurrence free survival	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

Name	Time	Method
Disease free survival	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.
Overall survival	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

Trial Locations

Locations (8)

Dr. B Barooah Cancer Institute; 🇮🇳 Guwahati, Assam, India

HCG Hospital; 🇮🇳 Ahmedabad, Gujarat, India

Tata Memorial Centre; 🇮🇳 Mumbai, Maharashtra, India

Sree Sankara Cancer Hospital; 🇮🇳 Bangalore, Karnataka, India

Amrita Institute of Medical Sciences; 🇮🇳 Kochi, Kerala, India

Mazumdar Shaw Medical Centre; 🇮🇳 Bangalore, Karnataka, India

Kailash Cancer Hospital and Research Centre; 🇮🇳 Goraj, Gujarat, India

Malabar Cancer Centre; 🇮🇳 Kannur, Kerala, India