Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:

Phase 3

Recruiting

• Conditions: Oral Cancer; Head and Neck Neoplasms

• Registration Number: NCT06737822
• Lead Sponsor: All India Institute of Medical Sciences, Jodhpur

Brief Summary

A majority of oral cancer patients in India present in the advanced stage hence tend to have poor oncological outcomes. Chemotherapy has been associated with improved oncological outcomes in various cancers but its role in oral cancer is not well defined in curative setting apart from radio sensitization. Attempted trials of neoadjuvant chemotherapy failed to show oncological advantage despite an excellent response rate, in part due to poor patient selection. Patients with a biologically aggressive disease are more likely to benefit, hence we intend to find out the oncological advantage of adding induction chemotherapy to oral squamous cell cancer with advanced nodal disease (N2-N3).

Earlier studies suffered from their heterogeneous patient population- all head and neck subsites together and included a spectrum ranging from early- stage operable cases to inoperable cancer. Due to such patient selection, the intended results were never met. The current study is intended to study the role of chemotherapy in curable patients who are most likely to benefit (biologically aggressive and advanced stage of presentation).

Objective

Primary:

To study the 2 year disease free survival by adding induction chemotherapy before surgery in patients of oral cancer with advanced nodal disease as compared to upfront surgery.

Secondary:

To assess treatment related outcomes between the treatment arms- Response rate; Treatment compliance; treatment related toxicity, postoperative complications and Quality of life.

To study the overall survival at 2 years. Oral cancer tissue biobanking for future translational research.

Study population Operable Oral cavity Squamous cell carcinoma with advanced nodal disease (N2-N3) Study Design Open label, Multi centric, randomized controlled trial with allocation ratio of 1:1

Sample Size The primary end point is disease-free survival. In order to have 80% power to detect a hazard ratio of 0.67, using a two-sided significance level, a total of 184 events are needed. Assuming an accrual rate of 15 patients a month, 300 patients need to be recruited. The analysis of DFS will take place 32 months after the start of the trial. The follow-up of patients will continue for 5 years. The analysis of OS will be conducted when 184 deaths are observed. taking 10% of withdrawal of consent, a total of 346 patients need to be included.

Inclusion Criteria Biopsy proven, operable oral Squamous cell carcinoma cT1-T4; cN2-N3, with adequate organ function, Age- 18-75 years, ECOG-PS:0-2 Treatment Arms

Standard Arm (SURG arm):

Surgery (Wide local Excision/composite resection with neck dissection) followed by adjuvant Radiotherapy ± Concurrent Chemotherapy

Experimental Arm (ICT):

2# TPF or TPX based induction chemotherapy followed by Surgery (Wide local Excision/composite resection with neck dissection) followed by adjuvant Radiotherapy ± Concurrent Chemotherapy

Study endpoints Primary- Disease free survival Secondary- Overall survival/ Quality of life/ Toxicity of treatment/ Treatment tolerance

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-07
• Study First Submitted QC: 2024-12-12
• Study First Posted: 2024-12-17
• Study Start: 2024-12-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-02
• Last Update Posted: 2025-03-04
• Primary Completion: 2027-10
• Study Completion: 2029-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 346

Inclusion Criteria

• Newly diagnosed, treatment naïve, biopsy or cytology proven OSCC
• Clinical Stage cT1-4a, cN2-N3**, M0- as per UICC 2018
• No evidence of distant metastases on chest x-ray and/or CT Thorax
• ECOG PS 0-2
• No contraindication to Cisplatin or radiotherapy***
• Patients eligible for definitive curative intent treatment after discussion in multidisciplinary tumour board
• Adequate organ function at time of participation, defined as Haematological: Haemoglobin > 9gm/dl, ANC ≥ 1500/cmm3, Platelet ≥100000/cmm3 Liver Function test: Bilirubin ≤2 x upper limit normal (ULN), AST/ALT/ ALP ≤ 2.5 x ULN Renal Function test: Creatinine ≤ 1.5 ULN, Creatinine Clearance ≥60 ml/min.

Exclusion Criteria

• Pregnant
• History of moderate to severe hearing loss.
• History of previous malignancy excluding non-melanoma skin cancers or cervical carcinoma in situ.
• Documented Weight loss of more than 15% in the last 6 months.
• Patients with known HIV, hepatitis B or C infection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Disease Free Survival	2 Years	Date of randomization to the date of clinical or pathological evidence of recurrence

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 Years	Date of randomization to the date of death due to any reason.
Treatment Completion Rate	2 Years	Number of Participants completing the treatment
Treatment Related Toxicity	2 Years	Chemotherapy Related and Radiotherapy Related: Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Quality of Life using PROs	3 Months; 6 Months; 12 Months; 18 Months; 24 Months; 36 Months; 48 Months; 60 Months	FACT HN Scale
Postoperative Surgical Morbidity	30 Days and 90 Days	Clavien Dindo Scale
Biobanking of Tumor, Non Tumor tissue and Blood	2 Years	DNA Sequencing using NGS to assess the genetic alterations
Financial Toxicity using Questionnaire	3 Months; 6 Months; 12 Months; 18 Months; 24 Months; 36 Months; 48 Months; 60 Months	FACT Scale
Early Radiotherapy Related Toxicity	30 Days	RTOG Criteria
Late Radiotherapy Relate Toxicity	2 Years	RTOG Criteria

Trial Locations

Locations (7)

All India Institute of Medical Sciences, Bhubaneshwar; 🇮🇳 Bhubaneshwar, Orisa, India

All India Institute of Medical Sciences, Jodhpur; 🇮🇳 Jodhpur, Rajasthan, India

All India Institute of Medical Sciences, Bathinda; 🇮🇳 Bathinda, India

Shri Mahant Indresh Hospital, Dehradun; 🇮🇳 Dehradun, India

King George's Medical University; 🇮🇳 Lucknow, India

All India Institute of Medical Sciences, Rishikesh; 🇮🇳 Rishīkesh, India

Geetanjali Medical College, Udaipur; 🇮🇳 Udaipur, India