Oral Cavity Carcinoma

This phase IV trial compares how well methadone plus standard fentanyl given during surgery (intraoperative) works compared to intraoperative standard fentanyl alone in managing pain after surgery (postoperative) among patients with head and neck cancers. For most head and neck cancers, the standard treatment is surgery to remove the cancer followed by surgical reconstruction, which often requires tissue harvested from another part of the body-known as a "free flap tissue transfer". These procedures are highly complex, demand a two-surgeon team, and often take many hours to complete. The combination of multiple operative sites and extent of the surgery contributes to significant postoperative pain. Methadone is not yet used in the head and neck population but has been utilized in other subspecialties like spine and cardiac surgery. The benefits of methadone may include improved pain control in the first 72 hours postoperatively requiring less opioids postoperatively and improvement in overall pain scores. Giving intraoperative methadone plus standard fentanyl may work better than fentanyl alone in managing postoperative pain among patients with head and neck cancers.

The goal of this clinical trial is to assess the safety and tolerability of a virus replicon particle (VRP) encapsulated saRNA encoding IL-12 when injected into in head and neck cancer patients. The main questions being addressed are: The safety and tolerability of intratumoral (IT) injections of VRP-encapsulated saRNA encoding IL-12 (VLPONC-01) The tumor response to IT injections of VLPONC-01 The tumor response due to the combination of IT injections of VLPONC-01 and system IV administration of neoadjuvant pembrolizumab (anti-PD-1) treatment Researchers will compare neoadjuvant pembrolizumab alone to the combination therapy to see if the combination enhances tumor responses.

This phase I, single-center study evaluates the safety, tolerability, and recommended phase II dose (RP2D) of mild hyperthermia (thermotherapy) when added to standard-of-care treatment in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). Tumor recurrence remains common despite chemoradiotherapy, highlighting the need for treatment intensification. Thermotherapy, which increases tumor temperature to 39-45°C, may enhance the effect of the treatment. The study consists of two components: (1) a dose-escalation cohort in patients receiving definitive chemoradiotherapy, using a Time-to-Event Bayesian Optimal Interval (TiTE-BOIN) design to determine the RP2D based on dose-limiting toxicities (DLTs) and treatment tolerability; and (2) a parallel cohort of patients receiving radiotherapy alone, in whom thermotherapy is administered at dose levels previously shown to be safe and tolerable in the chemoradiotherapy cohort to evaluate tolerability in this patient population. Besides the safety and tolerability of the thermotherapy RP2D, the secondary objectives include evaluation of safety in patients receiving radiotherapy alone, as well as exploratory assessment of tumor control and survival outcomes. This study aims to support the development of safe and feasible thermotherapy-based treatment strategies to improve locoregional control and outcomes in patients with LAHNSCC.

Patients with oral cavity cancer treated by reconstructive surgery with a flap. Patients will be treated in the study for : * Experimental arm: Post-operative radiotherapy with flap sparing * Control arm: Standard post-operative radiotherapy without flap sparing (current practice) Radiotherapy by IMRT using photons or proton therapy (IMPT)

This is a minimal risk intervention study where healthy volunteers and individuals with Fanconi anemia will consume a single dose of alcohol and provide primarily non-invasive biological samples at various time points. Biospecimens to be collected include saliva, oral cells collected via mouthwash and cheek brush, and urine. The collection of two blood samples (5 mL each) will be optional and banked for future use.

This Phase 3, multicenter, randomized, open-label study evaluates APG-157 in adults with newly diagnosed locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Two independently powered cohorts are enrolled based on treatment pathway. Cohort A evaluates APG-157 administered as neoadjuvant therapy before curative-intent surgery in participants with resectable oral cavity or oropharyngeal cancer who are medically ineligible for perioperative pembrolizumab. Cohort B evaluates APG-157 administered as induction therapy before definitive chemoradiotherapy and as maintenance therapy after chemoradiotherapy in participants with unresectable or medically inoperable disease. Participants are randomized 1:1 within each cohort to receive APG-157-based treatment or standard-of-care therapy. The primary hypothesis is that APG-157 given before definitive surgery followed by (chemo)radiotherapy improves event-free survival (EFS) compared to surgery and adjuvant (chemo)radiotherapy alone (Cohort A), and that APG-157 given as induction therapy prior to definitive chemoradiotherapy (CRT) followed by maintenance APG-157 improves EFS compared to definitive CRT alone (Cohort B).