Squamous Cell Carcinoma of the Larynx

To find the highest tolerable dose of stereotactic hypofractionated radioablation (HYDRA) radiation that can be given to patients with laryngeal cancer. The safety of this radiation will also be studied.

This randomized, prospective, multicenter phase II/III trial will study the reduction of radiation volume by eliminating radiotherapy (RT) to the elective neck using strictly defined surgical and radio-oncological standards to reduce radiotherapy-related long-term side effects without affecting locoregional control.

This is an open-label, single-dose, prospective clinical trial. The study comprises 2 work packages. The main objective of work package I (WP-1) is to assess feasibility of Fluorescence imaing (FLI) during total laryngectomy (TLE) and to assess the optimal dose of the cRGD-ZW800-1. Work package II (WP-II) is designed to assess whether FLI can detect and decrease tumor positive margins after a TLE.

Prospective, open, non-interventional, multi-center clinical registry study with the aim to establish a comprehensive research platform reflecting the real-world treatment landscape for recurrent/metastatic head and neck tumor patients.

ELOS is a prospective, randomized, open-label, controlled, two-armed parallel group, phase II multicentre trial in local advanced stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHNSCC) with PD-L1-expression within tumor tissue biopsy, calculated as CPS ≥ 1 curable by total laryngectomy. Induction chemotherapy (IC) with Docetaxel and Cisplatin (TP) followed by radiation will be compared to additional PD-1 inhibition. Patients will be selected after short induction early response evaluation after the first cycle IC (IC-1) aiming on larynx organ-preservation by additional 2 cycles IC followed by radiotherapy (69.6 Gy) for responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥ 30%. Nonresponders (ETSS \< 30% or progressing disease) will receive total laryngectomy and selective neck dissection followed by postoperative radiation or chemoradiation according to the recommendation of the clinics multidisciplinary tumor board. However, Patients randomized into the intervention arm starting day 1 will receive 200 mg Pembrolizumab (MK-3475) i.v. in 3-week cycle (q3w) for 17 cycles (12 months). Treatment with pembrolizumab will continue in the experimental arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent from subsequent decision on adjuvant therapy after TL.