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Multicenter Study
. 2024 Jun 1;25(6):1935-1943.
doi: 10.31557/APJCP.2024.25.6.1935.

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 Sunny  3 , Sruthi Nambiar  3 , Tinku Sarah  4 , Vaishnav Vasudevan  3 , Anusha Rao  3 , Anupama Murali  3 , Trupti Kolur  3 , Arvind Krishnamurthy  5 , Rajesh Kantharia  6 , Sudhir V Nair  7 , Krishnakumar Thankappan  8 , Baruah M N  9 , Rajeev Kumar  10 , Satheesan Balasubramanian  11 , Rajendra Toprani  12 , Sunil Agrawala  13 , Azar Jan Battoo  14 , Jaimanti Bakshi  15 , Sajith Babu  16 , Siddharth Shah  17 , Niravkumar Trivedi  18 , Sumithra Selvam  4 , Ravi Kannan  19 , Arun Kumar  3 , Amritha Suresh  20 , Vijay Pillai  3 , Pankaj Chaturvedi  7 , Subramania Iyer  8   21 , Moni Abraham Kuriakose  3
Affiliations
Multicenter Study

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

Vikram Kekatpure et al. Asian Pac J Cancer Prev. .

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.

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Conflict of interest statement

None of the authors have conflicts of interest to declare.

Figures

Figure 1
Figure 1
Combined Anti-Cancer Mechanisms of Curcumin and Metformin The Figure Depicts the Pathways that Curcumin and Metformin Target in the Cancer Cells.
Figure 2
Figure 2
Schematic Representation of the Study. The figure depicts a flowchart of the events in the trial. The patients are placed in a run-in period for a duration of 2 weeks before randomization to rule out any acute side effects. The patients will be recruited for the Phase IIB and subsequently in the Phase III of the trial. The primary and secondary endpoints of the trial are indicated.
See this image and copyright information in PMC

References

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