The rockefeller university

We are now recruiting for a phase I clinical trial testing the safety and tolerability of two drugs, metformin and naproxen, which have shown promise for reducing risk of head and neck squamous cell cancer.

Study title: A Randomized Crossover Open-Label Trial of Naproxen and Metformin Safety and Tolerability in the Setting of Prevention of Oral Cancer in Fanconi Anemia

Principal Investigator: Francis May, MD

Co-Principal Investigator: Agata Smogorzewska MD, PhD

Co-Principal Investigator: Rachel Uppgaard, DDS

Sites: The Rockefeller University, the University of Minnesota

Participants:  Adults with Fanconi anemia

Why are we performing this study?

Finding effective ways to slow down or prevent the development of cancer in individuals with Fanconi anemia (FA) is a critical medical priority. Individuals with FA are at dramatically higher risk of developing aggressive cancers, particularly of the head and neck, and these cancers are difficult to treat with standard therapies such as surgery, chemotherapy or radiation. Because options for treatment are limited and outcomes are often poor, prevention strategies are urgently needed.

What can you expect during the study?

• we will test two widely available drugs, metformin and naproxen, to evaluate whether they are safe and well-tolerated in patients with FA,
• a secondary aim of this study is evaluating how these drugs may lower the risk of cancer in FA patients
• Metformin is commonly prescribed for type 2 diabetes, while naproxen is a nonsteroidal anti-inflammatory drug (NSAID) frequently used for pain and inflammation.
• Both have shown potential in previous research to influence biological pathways linked to cancer development. By repurposing these well-known drugs, our trial aims to explore a safe, practical approach to cancer prevention in this at-risk population.

What will happen during a study site visit?

• At your site visits, we will examine your mouth and record it using a camera. We will collect cells using a brush from multiple locations in the mouth, both from normal-appearing areas in the mouth, and from abnormal looking areas (if any are present). We will look for changes in the cells’ appearance and genetic material (mutations). We will compare samples from FA participants to brush samples from healthy volunteers without FA.
• In addition, a blood sample (about two tablespoons) will be taken for genetic testing and additional cancer marker screening. A skin biopsy will be performed in FA participants post-bone marrow transplantation. Small surgical biopsies inside the mouth (5mm), about the size of a pencil eraser, will be taken at study visits, and analyzed by a pathologist for any cancerous or pre-cancerous changes. You will be randomized to receive either naproxen then metformin or metformin then naproxen for six months each. There is no placebo in this trial. During the study, you will be asked to fill out weekly surveys and have monthly televisits with study staff and oral self-exams to monitor for any negative effects of the drugs or new lesions, as well as two blood draws at a site local to you. The total number of visits to a study site is 5 per participant.
• Brush sampling allows for the easy, noninvasive collection of cells from the mouth, using a brush resembling a toothbrush, and can be used to sample multiple places in the mouth. The cells collected can be analyzed according to their appearance and for the presence of mutations. Once we investigate this technology, we hope it will aid in diagnosis of precancerous or cancerous cells and guide the need for a surgical biopsy.
• Surgical biopsy is the gold standard for identifying cancer or pre-cancerous changes in the mouth. By comparing the biopsy findings to the genetic findings, we hope the evidence from this study will help us use brushing in future studies as a less invasive sampling technique to identify early signs of cancer. We will provide detailed instructions on post-biopsy care.

Study Timeline. An overview of study design, with site visits at 0, 3, 9, 16 and 22 months.

Additional study information:

Full title: A Randomized Crossover Open-Label Trial of Naproxen and Metformin Safety and Tolerability in the Setting of Prevention of Oral Cancer in Fanconi Anemia

Study Location(s): The Rockefeller University in New York, NY and the University of Minnesota in Minneapolis, MN.

ClinicalTrials.gov #pending trial number and link

Funding: This study is funded by grant (#) from the Fanconi Cancer Foundation (https://fanconi.org/who-we-are/).