TPS12150 Background: Head and neck squamous cell carcinoma (HNSCC) is common in the Indian subcontinent and majority (65%) patients present in an advanced stage. Chemotherapy related cognitive impairment (CRCI) is a poorly defined and underestimated phenomenon in the HNSCC population. Through this study, we are attempting to establish evidence of activity of agents targeting neuro-inflammation in reducing or halting cognitive decline associated with definitive chemoradiotherapy for head and neck malignancies without adding to treatment-associated toxicity. This study can potentially aid in developing a cost effective approach with a readily available and cheap agent like celecoxib in improving the quality of life in this cohort of patients. Methods: This is a single center, double blinded placebo controlled phase 2 randomized trial. We intend to randomize 92 non metastatic HNSCC patients registered at a large tertiary cancer center of North India {Department of Medical Oncology (Head and Neck Cancer Clinic, All India Institute of Medical Sciences-National Cancer Institute, India)} planned for definitive chemoradiation (CTRT) with or without induction chemotherapy. Patients in the experimental arm will receive celecoxib 100 mg or matched placebo tablet orally twice a day starting with day 1 of initiation of definitive chemoradiotherapy/induction chemotherapy for a duration of 6 months or until unacceptable toxicity. Our primary objective is to determine the activity of celecoxib versus placebo in reducing cognitive decline in patients undergoing definitive CTRT with or without induction chemotherapy in HNSCC through patient reported outcome tools (FACT cog questionnaire). Secondary objectives include assessment of adverse event profile (measured using CTCAE v5.0), objective assessment of neurocognitive decline using neuropsychological battery of tests, to identify predictors of cognitive decline on the basis of site of malignancy, radiation dose to the base of skull and brainstem, age, comorbidities and educational status. Tertiary objective include evaluation of inflammatory biomarkers e.g serum COX-2, serum Interleukin and tumor necrosis factors-alpha levels at the end of therapy and on follow up. Clinical trial information: CTRI/2022/09/045579.