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

Asian Pac J Cancer Prev. 2024 Jun 1;25(6):1935-1943. doi: 10.31557/APJCP.2024.25.6.1935.

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 to a 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 of SPT, 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: Keywords: Head and Neck Squamous cell Carcinoma; Metformin; Second Primary Tumour; curcumin.

Publication types

  • Clinical Trial Protocol
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Curcumin* / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / prevention & control
  • Humans
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Multicenter Studies as Topic
  • Neoplasms, Second Primary* / prevention & control
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Research Design
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / prevention & control

Substances

  • Curcumin
  • Metformin