Squamous Cell Carcinoma

This research study is testing whether a new study drug (called ATRN-119) is safe and effective when combined with a single, highly targeted dose of radiation therapy (called stereotactic body radiation therapy or SBRT) to treat early-stage throat cancer that is caused by HPV. The goal of this study is to treat cancer effectively while reducing side effects and helping patients maintain a better quality of life over the long term. Researchers hope that this approach will be just as successful-or possibly more successful-than current treatments, which already have high cure rates. Participants will: * Take 800mg of ATRN-119 every day for 10 days * Receive 1 treatment (called a "fraction") of SBRT to the neck on day 3 of ATRN-119 dosing. * Keep a short diary to track ATRN-119 dosing. The diary will be provided by study team * Receive standard of care treatment after treatment with ATRN-119 + SBRT including TransOral Robotic Surgery (TORS) to remove the primary tumor with Neck Dissection and adjuvant therapy (if indicated) * Receive additional safety checkups and tests by researchers during routine visits with their cancer doctor for 2 years after study treatment

This single-arm Phase II trial evaluates whether omission of postoperative radiotherapy is feasible and oncologically safe in select patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC). Eligible patients undergo transoral robotic surgery (TORS) and are observed without adjuvant radiation if they demonstrate low or intermediate pathological risk features and have negative circulating tumor HPV DNA (ctHPVDNA) two weeks post-operatively. Patients are followed with standard clinical surveillance combined with serial ctHPVDNA testing (NavDx®) to facilitate early detection of recurrence and prompt salvage therapy as needed.

This research study is for people who have been diagnosed with a nonmelanoma skin cancer (either basal cell carcinoma or squamous cell carcinoma) and are planning to receive either Mohs surgery or ED\&C (electrodessication \& curettage) as part of clinical care. The purpose of this study is to understand how photodynamic therapy (PDT) with or without Vitamin D can promote an immune response to skin cancer. For this study, participants will be randomized (randomly assigned) and asked to take Vitamin D or placebo for 6 days and come to the clinic for a single PDT treatment 1-14 days prior to their surgery. At this visit, photographs of participant's skin cancer will be taken, and participants will undergo PDT treatment. The study team will also take photos on the day of Mohs surgery or ED\&C. There will be up to two blood draws for research. If participants do not want to come in for a PDT treatment prior to their Mohs surgery or ED\&C, they will have the option to participate by only allowing the study team to collect data about their skin cancer and their tissue from Mohs surgery or ED\&C.

This is a multi-center clinical study enrolling up to 28 participants. The primary objectives are to determine the objective response rate (ORR) established by the confirmed best overall response (BOR) following intratumoral administration of DaRT - Diffusing Alpha-Emitters Radiation Therapy. Secondary objectives are to: 1. Determine Progression Free Survival (PFS) up to 12 months after Alpha DaRT sources insertion. 2. Assess Overall Survival (OS) of patients treated with DaRT up to 12 months. 3. Assess Local control up to 12 months after DaRT insertion.

In squamous cell carcinoma of the tongue, complete surgical resection of the tumor generally represents the primary treatment strategy. Among factors determining the disease prognostic, the surgical margins status is essential for the continued management of the patient, with or without complementary therapies. Generally, surgical margins are defined using visual and tactile elements. Unfortunately, in 15 to 30 percent of cases, they are defined as positive after histopathological examination, on average 5 to 7 days post-surgery. Techniques have recently been developed to analyze the cancerous and non-cancerous nature of tissues, using the spectral properties of tumor cells. SpiderMass™ is an instrument equipped with a probe for tissue micro-sampling and real-time molecular profile analysis. It is thus ultimately a tool for anatomopathological decision support, for diagnosis and prognosis of the disease. Used in the operating room, SpiderMass™ could also become an innovative surgical tool to precisely define cancerous areas in situ and the margins status in intraoperative conditions. Based on the principle of artificial intelligence, the SpiderMass™ machine must initially learn to recognize pathological tissues versus healthy. This project aims to accomplish this first phase of machine learning for squamous cell carcinoma of the tongue.

This is a phase 1, single-arm, open-label, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of TGFBR2 TROP2 CAR/IL15 NK cells in patients with high-risk oral premalignant lesions.

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe. Eligibility: \- Adults age 18-72 with NSCLC who have a tumor that can be safely removed. Design: * Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. * Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

This is a pilot clinical trial determining the effect of a Methionine-reduced diet on serum levels in subjects with solid tumors. These are subjects who will receive systemic standard of care cancer therapy.

This is a Phase Ib/II multi-center, open-label study of HMBD-001 in combination with cetuximab with or without docetaxel in participants with advanced Squamous Cell Cancers

This clinical study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of IDP-001 in participants with advanced or metastatic squamous and non-squamous NSCLC and other squamous cell solid tumors (for example, head and neck, esophageal, cervical, cutaneous).

This phase II trial studies whether providing cancer treatment in the home is preferred over the traditional clinic setting and if it improves treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas. Typically, drug-related cancer care is provided at a medical center which causes patients to have to spend considerable time away from their family, friends, and familiar surroundings. This may add to the physical, emotional, social, and financial burden for patients and their families during this difficult time in their lives. The Cancer Connected Access and Remote Expertise (CARE) Beyond Walls (CCBW) program uses a specialized care team trained to provide cancer treatment in the patient's home setting. It is designed to support remote connection between the home health team and providers and Mayo clinic. This may be preferred over the traditional clinic setting which may improve treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas.

This is a prospective observational clinical study designed to evaluate the performance of artificial intelligence (AI) algorithms applied to upper aerodigestive tract (UADT) video-endoscopy. The study assesses three main tasks: lesion detection (localization), classification (benign vs malignant), and segmentation of tumor margins. AI algorithms will be applied to endoscopic video data acquired during routine clinical practice without influencing clinical decision-making. The system will process images in real time and store data for subsequent analysis. AI outputs will be compared with physician assessment and reference standard histopathology to evaluate diagnostic performance.

Based on evidence that the local anesthetic lidocaine may have anticancer effects, this study will assess the safety and efficacy of intratumoral lidocaine injection at the time of direct laryngoscopy prior to TransOral Robotic Surgery (TORS) and neck dissection for oropharyngeal squamous cell carcinoma (OPSCC). The primary objective of the study is to determine if intratumoral lidocaine injection is safe and causes a major pathologic treatment effect in the primary tumor following surgical resection. The secondary objectives will be to determine if intratumoral lidocaine injection improves locoregional control rates, progression-free survival, metastasis-free survival, and overall survival compared to no injection.

This study aims to learn more about anal cancer risk in men who have sex with men (MSM) who are using Pre-Exposure Prophylaxis (PrEP) to prevent HIV. Specifically, we want to check how common High-Grade Squamous Intraepithelial Lesions (HSIL) are in this group, how well anal swabs can screen for these lesions, and how having HSIL affects their quality of life. We'll also test if DNA methylation testing can give us extra information about the lesions. The main questions the study aims to answer are: * How common are HSIL in MSM using PrEP? * How accurate are anal swabs for detecting HSIL in this group? * How does having HSIL affect the quality of life of MSM using PrEP? * Can DNA methylation testing help improve our understanding of HSIL in these individuals? Participants will: * Answer questions about their health and quality of life. * Have an anal smear collected for testing. * Undergo High-Resolution Anoscopy (HRA) to check for HSIL and get a biopsy if deemed necessary.

The goal of this observational study is to find out if Raman Spectroscopy, a type of imaging, can be used to determine the size of skin cancer tumors. The main question it aims to answer is: -Can Raman Spectroscopy help figure out how far a tumor spreads? This study will take measurements using laser light from an experimental, handheld probe by lightly touching the skin.

The NeoScorch HN study is a single institution multisite phase II trial including 3 cohorts of 25 patients each for patients with newly diagnosed locoregionally advanced, histologically confirmed, head and neck cancer eligible for curative-intent treatment, who will receive neo-adjuvant chemoimmunotherapy-based treatment as well as standard of care adjuvant treatment. The three cohorts include three different aspects of surgical de-escalation in head and neck cancer. The first cohort includes human papillomavirus independent (HPV-) squamous cell carcinoma of the head and neck. The second cohort includes HPV-associated head and neck cancer with radiographic evidence of extranodal extension in neck lymphadenopathy. The third cohort specifically includes malignancies of the sinonasal cavity and skull base which have a propensity for invasion of the orbit, skull base, and maxilla. Surgical treatment of all three of these cohorts has significant morbidity including swallowing, speech, and vision among others.

The study objective is to see if BVEC induced C7 expression in Recessive Dystrophic Epidermolysis Bullosa (RDEB) skin following Squamous cell carcinoma (SCC) excision will normalize the invasive tumor microenvironment and reduce tumor recurrence. Prevention of SCC's in the RDEB subjects will increase their life span.

The goal of this clinical trial is to learn if drugs as cyclophosphamide (C) and etoposide (E) work to treat advanced head and neck cancer in adults. It will also learn about the safety of both drugs. The main questions it aims to answer are: Do drugs C and E work to treat advanced head and neck cancer, after failure on first line chemotherapy? What medical problems do participants have when taking drugs C and E? Researchers will compare drugs C and E in combination to a placebo (a look-alike substance that contains no drug) to see if these 2 drugs works to treat advanced head and neck cancer. Participants will: Take drug C every 3 weeks and drug E every 4 weeks or a placebo every week for 6 months. Visit the clinic once every 3 weeks for checkups and tests. Keep a diary of their symptoms.

The study will evaluate patient and Health Care Professional- reported preference for Subcutaneous (SC) compared with IV nivolumab administration or similarly for SC compared with IV pembrolizumab.

The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC). The side effects of these combinations will also be studied. This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status and the presence of ERCC-1 \[4F9\] in the tumor prior to randomization. The study will evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which radiation and chemotherapy combination works best in relationship to how much ERCC-1 \[4F9\] is expressed in a tumor.

This is an monocenter, single arm, clinical investigation that evaluate the impact of the method on the objective response rate (ORR) of visceral lesions undergoing electrochemotherapy. Electrochemotherapy is a well-defined method for the treatment of cutaneous and subcutaneous metastases of different tumor histotypes. Although still limited, the various experiences in the treatment of visceral localizations, particularly in liver metastases from colorectal cancer are promising and show that electrochemotherapy is a safe treatment, even in the case of lesions near large vessels or nerves. The investigators therefore propose a clinical investigation with a Medical Device according to EU Regulation 745/2017, using electrochemotherapy (Cliniporator) with bleomycin for the treatment of visceral, primary or secondary, unresectable localizations, with percutaneous or intraoperative technique (laparoscopic or laparotomy), as needed.

VET3-TGI is an oncolytic immunotherapy designed to treat advanced cancers. VET3-TGI has not been given to human patients yet, and the current study is designed to find a safe and effective dose of VET3-TGI when administered by direct injection into tumor(s) (called an intratumoral injection) or when given intravenously (into the vein) both alone and in combination with atezolizumab in patients with solid tumors (STEALTH-001).

The purpose of the study is to determine if it is feasible to use magnetic resonance imaging (MRI) to adjust a portion of radiation therapy for patients with head and neck squamous cell carcinoma . The technique under study will be used to personalize the study treatment based on response, keeping all treatments within standard of care guidelines.

This is a single arm phase II study that will evaluate the combination of pembrolizumab, docetaxel, and cisplatin or carboplatin (PDC) as single treatment modality in patients with stage II-IVb (T2-4, any N, M0) squamous cell carcinoma of the nasal cavity/paranasal sinuses (PNS SCC).

Survival after cancer diagnosis strongly depends on local tumor extent, lymph node involvement and the presence of distant metastases. However, there remains great inter-patient variability regarding treatment outcome. A combination of molecular factors, biochemical factors, histopathological features, genomic profile, environmental factors and other clinical factors are likely to influence prognosis and treatment effect, independent from tumor stage. It is however still unclear which, how, and to what extent these factors will influence tumor recurrence and mortality in both early stage (I-III) and late stage (IV) thoracic malignancies such as lung cancer. Although the results from prospective clinical trials will remain the backbone of evidence-based medicine, this concerns a highly selected patient population since the large majority (85%-95%) of patients with cancer do not participate in clinical trials for various reasons. It is unlikely that trial participation will significantly improve in the near future. This fact has the following implications: 1. It is highly desirable to validate the results from clinical trials in the general patient population. This is complicated by the fact that the documentation of patients treated in general practice (i.e. outside the scope of clinical trials) is largely insufficient to provide comparable patient cohorts in terms of prognostic characteristics and treatment parameters. 2. There is an ever increasing number of therapeutic interventions available for which its efficacy depends on known and unknown tumor-specific, clinical, demographic and other patient characteristics. Large numbers of patients are required to test the relevance of these variables. 3. As a result of rapid technical and drug developments, new minimally invasive treatment options such as stereotactic irradiation or ablation techniques or sublobar resections and new targeted and immunotherapeutic treatments have entered the clinic. These interventions have potentially less side effects compared to the conventional treatments. Still, these new interventions will have to prove their effectiveness, safety and superiority (or non-inferiority) in a real world setting. 4. Many hypotheses related to further optimization of personalized medicine can currently not be tested as they require a large prospective cohort of patients, and a less time-consuming and costly research infrastructure. A prospective observational cohort study has the potential to fill the gap between prospective randomized trials (efficacy) and patients treated in general practice (effectiveness) and it will enable accrual of clinical trials (innovation).