Clinical Research Directory

Safety and Tolerability of Metformin and Naproxen for Cancer Prevention in Fanconi Anemia

Finding effective ways to slow down or prevent the development of cancer in people 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. In this study, the investigators will test two widely available drugs, metformin and naproxen, to evaluate whether they can 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, this trial aims to explore a safe, practical approach to cancer prevention in this vulnerable population. The study, conducted at the Rockefeller University and the University of Minnesota, has several goals. First, the investigators will carefully assess the safety and tolerability of metformin and naproxen when used in participants with FA. Because these individuals can be more susceptible to metabolic disorders like diabetes compared to the general population, and may have genitourinary abnormalities related to their underlying condition, monitoring for side effects and adverse events is especially important. Second, investigators will evaluate whether intervention affects visible or microscopic changes in the mouth, where cancers often arise. This will involve performing small biopsies of oral tissue to look for cancerous or pre-cancerous lesions. Third, investigators will investigate early molecular changes using an exploratory less invasive technique: collecting cells with a soft brush, similar to a toothbrush. These samples will allow the investigators to analyze biomarkers-biological signals that can indicate increased or reduced cancer risk-before and after intervention. Together, these approaches will provide information on whether metformin or naproxen are safe and well-tolerated in the FA population. As an additional outcome, by combining direct tissue analysis with biomarker studies, the investigators aim to detect subtle changes that precede cancer, giving us an early indication of whether the drugs are working as preventive agents. Although this is an early-phase study, its potential significance is considerable. Demonstrating that well-tolerated, inexpensive, and widely accessible drugs may have potential to reduce cancer risk would represent a major advance for FA patients, who currently face limited options for prevention and treatment. This work may also offer insights relevant to broader cancer prevention efforts in other high-risk groups. Ultimately, our study seeks to take an important step toward changing the outlook for people with Fanconi anemia by moving the focus from late-stage treatment toward early prevention.

Safety and Feasibility of Nivolumab-IRDye800CW in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)

The goal of this Phase 1 clinical trial is to evaluate the safety and feasibility of nivolumab-IRDye800CW (nivo800) as a molecular imaging agent in adults with biopsy-confirmed or presumed head and neck squamous cell carcinoma (HNSCC) who are scheduled to undergo standard-of-care surgical resection. The main questions it aims to answer are: * Is nivolumab-IRDye800CW (nivo800) safe when administered before surgery, as measured by the occurrence of clinically significant Grade ≥2 adverse events that are possibly, probably, or definitely related to the study drug? * What is the extent of pathological response at each dose level, including residual viable tumor, fibrosis, necrosis, and tumor-infiltrating lymphocyte characteristics? Participants will: * Receive two intravenous infusions during the preoperative period, approximately 2-3 weeks before surgery and again 1-2 days before surgery. * Undergo standard-of-care surgical resection with collection of tumor and lymph node specimens for pathological and imaging studies.

A Study of TAK-186 (Also Known as MVC-101) in Adults With Advanced or Metastatic Cancer

The main aim of this study is to check for side effects and tolerability of TAK-186 (also known as MVC-101) in adults with unremovable advanced or metastatic cancer. Another aim is to characterize and evaluate the activity of TAK-186 (MVC-101). Participants may receive treatment throughout the study for a maximum of 13 months and will be followed up at 30 days and 90 days and then every 12 weeks for up to 48 weeks after the last treatment.

Skin Cancer Among Outdoor Workers

This observational study examines skin cancer among workers who may have prolonged occupational exposure to sunlight. Long-term exposure to ultraviolet radiation from the sun is an important risk factor for several types of skin cancer, particularly among people who work outdoors for many years. The study will use routinely collected administrative and medical data to describe the characteristics of workers with recognized skin cancer, including age, sex, geographic region, type of skin cancer, occupational characteristics, and disability-related outcomes. Trends over time and differences between population groups will also be evaluated when the available data permit. The purpose of the study is to better understand the burden of skin cancer associated with occupational sun exposure and to identify groups of workers who may be at increased risk. The findings may help support improved prevention, earlier detection, workplace sun-protection measures, and occupational health policies for outdoor workers.

Tumoral Versus Luminal Microbiome in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC), France's 5th most common cancer (15,000 annual cases), presents significant public health challenges due to high morbidity and functional/aesthetic sequelae from treatments (mutilating surgery, radiotherapy, chemotherapy). Major risk factors, tobacco and alcohol, create a chronic inflammatory environment promoting tumor development. The upper aerodigestive tract microbiome, influenced by these exposures and local alterations (necrosis, bleeding, ulcerations), is emerging as a potential factor in tumor progression, severity biomarker, or therapeutic target, though its exact role (cause or consequence) remains to be elucidated Objectives: * Primary: Compare bacterial microbiome composition between tumor tissue, adjacent healthy mucosa, and pharyngeal secretions * Secondary: * Correlate microbiome diversity/composition with clinical and epidemiological characteristics * Identify microbiome variations by tumor stage, histology, and infiltration * Discover diagnostic/prognostic microbial markers * Analyze somatic variants (SNP/CNV) via whole-genome sequencing (WGS) and their association with microbiome profiles and clinical parameters Study Design: Prospective, cross-sectional study with paired design (each patient serves as their own control to minimize genetic variation biases) Methods: * Samples: Tumor, adjacent healthy tissue, and pharyngeal secretions (3 samples/patient) * Sequencing: Metagenomic sequencing (complete bacterial genomes) when biomass permits, or targeted 16S rRNA sequencing to identify dominant genera. * Pilot study: 20 patients to select the optimal technique and validate feasibility, particularly assessing DNA quantity in these low-biomass environments Population: Adults with suspected HNSCC scheduled for panendoscopy Exclusion criteria: Recent antibiotics/corticosteroids (12 weeks), immunosuppression (uncontrolled HIV, active hematologic malignancies, autoimmune diseases on immunosuppressants, organ/stem cell transplants, uncontrolled diabetes), immunomodulatory treatments (3 months), recurrence, pregnancy, non-French speakers, legal guardianship, or lack of social security. Safety: No additional risks beyond standard panendoscopy. Expected impact: This approach may pave the way for innovative diagnostic or therapeutic strategies based on microbiome modulation in HNSCC.

Comparing Postoperative Adjuvant Cisplatin Concurrent Chemoradiotherapy With Adjuvant Radiotherapy Alone for Intermediate-risk Head and Neck Squamous Cell Carcinoma

The main objective of this trial was to determine the value of concurrent chemoradiotherapy for Intermediate-risk head and neck squamous cell carcinoma

Phase II Study of Daily Adaptive Radiotherapy for Submandibular Gland-sparing in Head and Neck Cancer

This is a randomized, single centre, single blinded prospective study comparing the standard of care imaging guided radiation therapy and daily adaptive radiotherapy (ART) for submandibular gland-sparing in head and neck cancer

Stereotactic MRI-guided Focused Ultrasound Mesencephalotomy

This phase 1 multi-site study investigates the safety and initial effectiveness of focused ultrasound lesioning of the contralateral mesencephalon for severe, opioid-resistant pain associated with head and neck cancer and brachial cancer.

Multimodal Prediction of Response to Chemoradiotherapy for Squamous Cell Carcinoma of the Head and Neck

The goal of the study lies in offering a multimodal analysis of the post-therapeutic response based on both quantitative parameters and radiomics (CT, MRI, and PET imaging), and on tumor biology, in particular the hypersensitive detection of tumor DNA.