Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial

Sep 21, 2026

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The study outlines a clinical-trial protocol that uses a 2x2 factorial design to evaluate Metformin and Curcumin for preventing second primary tumors in patients previously treated for head and neck squamous cell carcinoma (HNSCC). It leverages strong preclinical evidence without substantially increasing sample size, enabling multiple comparisons and interaction assessment. The randomized, double-blind, multi-centric, placebo-controlled trial enrolls 1,500 participants and treats for 36 months, with safety, efficacy, recurrence, and biomarker-related outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Introduction

RESEARCH ARTICLE Editorial Process: Submission:09/05/2023 Acceptance:06/10/2024 Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial Vikram Kekatpure 1, Narayana Subramaniam 2, Sumsum Sunny3, Sruthi Nambiar3, Tinku Sarah4, Vaishnav Vasudevan3, Anusha Rao3, Anupama Murali3, Trupti Kolur3, Arvind Krishnamurthy5, Rajesh Kantharia6, Sudhir V Nair7, Krishnakumar Thankappan8, Baruah M N9, Rajeev Kumar10, Satheesan Balasubramanian11, Rajendra Toprani12, Sunil Agrawala13, Azar Jan Battoo14, Jaimanti Bakshi15, Sajith Babu16, Siddharth Shah17, Niravkumar Trivedi18, Sumithra Selvam4, Ravi Kannan19, Arun Kumar3, Amritha Suresh20, Vijay Pillai3, Pankaj Chaturvedi7, Subramania Iyer8,21, Moni Abraham Kuriakose3 * Abstract Objective: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. Methods: We have applied the trial design toa large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274] . Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development ofSPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. Conclusion: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly. Keywords: Head and neck squamous cell carcinoma-second primary tumour-curcumin-metformin Asian Pac J Cancer Prev, 25 (6), 1935-1943 1Department of Head Neck Oncology, Cytecare Cancer Hospital, Bangalore, India. 2Department of Head and Neck Oncology, Sri Shnakara Caner Foundation, Bangalore, India. 3Department of Head and Neck Oncology, Mazumdar Medical Center, Narayana Health City, Bangalore, India. 4St. Johns’ Research Institute, Banglore, India. 5Department of Head and Neck and Thoracic Oncology, Cancer Institute, Adyar, Chennai, India. 6Department of Head and Neck Oncosurgery, Kailash Cancer Hospital and Research center, Goraj, Vadodara, India. 7Department of Head and Neck Surgical Oncology, Tata Memorial Center, Navi Mumbai, Maharashtra, India. 8Department of Head Neck Surgery and Oncology, Amrita Institute of Medical Science and Research Centre, Kochi, Kerala, India. 9Head and Neck Oncology, Managing Director & Research Head, NorthEast Cancer Hospital and Research Institute, Assam. 10 Otorhinolaryngology and Head-Neck Surgery, Professor, All India Institute of Medical Sciences, Delhi, India. 11Department of Surgical Oncology, Malabar Cancer Centre, Thalassery, Kerala, India. 12Department of Head and Neck Cancer, HCG Cancer Centre, Ahmedabad, India. 13Department of Surgical Oncology, Professor, IMS & SUM Hospital, Bhubaneswar, India. 14Surgical Oncology, Associate Professor, Sher-i-Kashmir Institute of Medical Science, Srinagar, India. 15Department of Otolaryngology, Professor and Head, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 16Surgical Oncology, Associate Professor

FAQs

What is the main objective of the trial protocol?

To describe a protocol for applying Metformin and Curcumin in preventing second primary tumors after treatment of HNSCC, using a 2x2 factorial design to compare interventions efficiently.

How was the trial designed and what is the study population size?

The trial uses a 2x2 factorial design in a large phase IIB/III double-blind, multi-centric, placebo-controlled randomized clinical trial with 1,500 participants.

What are the primary and key secondary endpoints?

The primary endpoint is development of second primary tumors (SPT). Secondary endpoints include treatment-associated toxicities, incidence of recurrence, and identification of potential biomarkers.

Sep 21, 2026

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