Squamous Cell Carcinoma of the Head and Neck

Standard radiotherapy for head and neck squamous cell carcinoma typically requires daily treatments over 6 to 7 weeks. For older adults, these prolonged treatment schedules can cause substantial physical fatigue, travel burden, and treatment interruptions. Hypofractionated radiotherapy delivers higher doses of radiation per session over a shorter total treatment time (approximately 3 weeks), potentially limiting tumor cell regrowth, easing logistical demands on patients, and improving completion rates. The purpose of this randomized controlled trial is to evaluate the clinical effectiveness, safety, and toxicity of hypofractionated radiotherapy compared with standard normofractionated radiotherapy in older adults with non-metastatic head and neck squamous cell carcinoma. Eligible participants aged 65 years and older will be randomly assigned in a 1:1 ratio to receive either: * Hypofractionated Radiotherapy (Intervention): External beam radiotherapy delivered via image-guided intensity-modulated techniques (IMRT/VMAT) once daily over approximately 3 weeks (45 Gy in 15 fractions for definitive therapy, or 40.5 Gy in 15 fractions for postoperative/adjuvant therapy). * Standard Normofractionated Radiotherapy (Comparator): External beam radiotherapy delivered once daily using conventional fractionation schedules over approximately 6 to 7 weeks according to institutional clinical standards. Participants will be monitored weekly during radiation treatment and followed for up to 1 year post-treatment. The primary outcome is locoregional control, with secondary outcomes assessing overall survival, disease-free survival, acute and late toxicities graded by CTCAE version 6.0, and health-related quality of life.

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.

The purpose of ORACLE is to demonstrate the ability of a novel ctDNA assay developed by Guardant Health to detect recurrence in individuals treated for early-stage solid tumors. It is necessary that ctDNA test results are linked to clinical outcomes in order to demonstrate clinical validity for recurrence detection and explore its value in a healthcare environment subject to cost containment.

The objective of this study is to compare the efficacy and safety of MRG003 versus cetuximab/methotrexate as second/third line of therapy in patients with RM-SCCHN who have previously failed PD-1 (L1) inhibitors and platinum-based therapy.

This study will test the safety of a drug called PF-08046054/SGN-PDL1V alone and with pembrolizumab in participants with solid tumors. It will also study the side effects of this drug. A side effect is anything a drug does to your body besides treating your disease. Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable). This study will have five parts. Parts A and B of the study will find out how much PF-08046054/SGN- PDL1V should be given to participants. Part C will use the dose found in Parts A and B to find out how safe PF-08046054/SGN-PDL1V is and if it works to treat solid tumor cancers. In Part D and E, participants will be given PF-08046054/SGN-PDL1V with pembrolizumab to find out how safe this combination is and if it works to treat solid tumor cancers.

This trial is to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab prior to surgical resection in participants with resectable, high-risk, locoregionally advanced, PD-L1-positive squamous cell carcinoma of the head and neck (HNSCC). The names of the study drugs used in this research study are: * ficerafusp alfa (a type of bifunctional antibody and recombinant fusion protein) * pembrolizumab (a type of monoclonal antibody)

This is a multicenter, randomized, open-label, non-inferiority clinical trial designed to evaluate whether downgraded surgery-guided by post-immunotherapy tumor boundaries-can achieve comparable 3-year overall survival (OS) to standard surgery in patients with Stage III-IVa locally advanced head and neck squamous cell carcinoma (HNSCC) who have responded to neoadjuvant immunotherapy. A total of 356 patients will be randomized 1:1 to receive either downgraded or standard surgery, followed by risk-adapted adjuvant therapy. The primary endpoint is 3-year OS, with secondary endpoints including disease-free survival, quality of life, complication rates, and cost-effectiveness. The study hypothesizes that downgraded surgery will preserve organ function and quality of life without compromising survival outcomes.

The main objectives of this study are to assess the safety, tolerability, immunological activity, and preliminary efficacy of the Modi-1 Moditope vaccine, both as monotherapy and in combination with a checkpoint inhibitor (CPI) such as pembrolizumab or nivolumab with or without Ipilimumab (where these are standard of care in a non-neoadjuvant setting), in patients with advanced triple negative breast cancer (TNBC), advanced/unresectable human papillomavirus-negative squamous cell carcinoma of the head and neck (SCCHN), high grade serous ovarian carcinoma (HGSOC), or renal cell carcinoma (RCC). Modi-1 Moditope will also be investigated in the neoadjuvant setting for patients with SCCHN undergoing curative intent surgical resection in combination with pembrolizumab versus the Modi-1 alone.

This is a multicentric, retrospective, and prospective biomarker study.

The goal of this observational study is to learn about the occurrence of and to identify suitable strategies for screening and monitoring of inner ear damage in patients receiving cisplatin chemoradiotherapy for head and neck cancer. Researchers will compare patients who are receiving cisplatin chemoradiotherapy to patients who are only receiving radiotherapy. Patients will undergo standardized testing for hearing loss, tinnitus and vestibular dysfunction at baseline, during and after treatment. Optional genetic analyses will aim to identify genes known to predispose to cisplatin-induced ototoxicity.

This study is a Phase 2, double-blind, randomized controlled trial evaluating the safety and efficacy of TV5M01 (a 5% green tea and 0.1% morphine gel) compared to triple mixture (0.19% lidocaine, 0.29% nystatin, and 5.50% hydroxides) for treating radiation-induced oral mucositis in patients with head and neck squamous cell carcinoma. The trial will enroll 40 patients (20 per group) with stage III-IV head and neck cancer receiving radiotherapy who develop grade 1 or higher mucositis. Participants will apply the assigned mouthwash three times daily from mucositis diagnosis until resolution. Primary outcomes include safety (incidence of infections and adverse events) and efficacy (duration of grade 3-4 mucositis, days with severe pain). Secondary outcomes include quality of life and analgesic use. Randomization will use minimization methodology to balance important prognostic factors. The study design incorporates two interim analyses after 10 and 19 participants, with clear safety monitoring and stopping rules. If successful, this trial could provide an evidence-based treatment option for radiotherapy-induced mucositis, potentially improving treatment completion rates and quality of life for head and neck cancer patients.

Patients with locally recurrent squamous-cell carcinoma of the head and neck (SCCHN) after Chemotherapy and immunotherapy have a very poor prognosis and limited therapeutic options. Intratumoral chemotherapy (ITC) with cisplatin and epinephrine in order to increase the local cisplatin retention lead to a 50 % response rate in several studies but was given up due to the poor local tolerance with frequent necrosis of the peritumoral tissues. Gemcitabine, carboplatin and paclitaxel (GCP) are used in advanced SCCHN. These chemotherapies seem to be interesting options for intratumoral infusion: their different effect could lead to avoid chemotherapy resistance with a good tolerance profile, without tissue necrosis profile. The other major option for recurrent SCCHN is immunotherapy by Nivolumab, an anti PD-1 with a 13% mediane response rate. Nevertheless, the failure of this treatment stay unclear, but immunosuppressive action of the tumour is suspected. The presence of tumoral antigen could lead to better response to immunotherapy; association of chemotherapy and immunotherapy seems a promosing association to avoid treatment resistance as cytotoxic release tumoral antigen; it could also be associated to an abscopal effect. The aim of the study is to evaluate the efficacy of ITC using GCP in LOCAL recurrent SCCHN treated by nivolumab.

The investigators want to have a collection of fresh primary or recurrent tumor tissue for establishment of patients-derived xenografts in order to: generate a biobank of in vivo patient xenografts representing the different subgroups of tumors for head and neck cancer * perform genetic and transcriptional profiling of the primary, metastatic tumors and xenograft tumors * evaluate the efficacy of new targeted agents, whether or not in combination with standard treatment options * evaluate biomarkers of drug sensitivity * study primary and secondary (acquired) resistance in these models

This is a multiphase, multicenter study, which includes a Phase 1a open-label, dose escalation monotherapy study of ST-067 given as an SC injection with or without obinutuzumab \[Gazyva®\] pre-treatment, by IV infusion, and in combination with pembrolizumab. A Phase 2 monotherapy arm is also planned; the exact design of the Phase 2 study elements with respect to formulation and pre-treatment will be determined after completion of the Phase 1 study portion of the trial.

The investigators will collect plasma samples at baseline, during treatment, and at progression.