<strong>OBJECTIVES</strong> The trial objectives will be assessed within each patient cohort as defined below: <ul> <li>Non-OPC/p16-negative OPC Cohort: Patients with laryngeal and hypopharyngeal cancer: T3-4 N0, T1-4 N1-3, or T2N0 (hypopharynx only). Patients with oropharyngeal cancer and p16-negative: T2N1, T1-4 N2-3, or T3-4 N0-1.</li> <li>p16-positive OPC/CUP Cohort: Patients with oropharyngeal cancer and p16-positive: ≤ 10 pack-years and T1-3 N2-3 or T4 N0-3; > 10 pack-years and T1-2 N2-3 or T3-4 N0-3. Patients with cancer of unknown primary and p16-positive: T0 N2-3 are included.</li> </ul> <u><strong>Primary Objectives</strong></u> <ul> <li>Phase II: <ul> <li>To determine whether radiation with low-dose cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with high-dose cisplatin every 3 weeks for patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN).</li> </ul> </li> <li>Phase III: <ul> <li>To determine whether radiation with low-dose cisplatin weekly is non-inferior to radiation with high-dose cisplatin every 3 weeks in terms of overall survival (OS) for patients with locoregionally advanced SCCHN.</li> <li>To determine whether radiation with low-dose cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with high-dose cisplatin every 3 weeks for patients with locoregionally advanced SCCHN.</li> </ul> </li> </ul> <u><strong>Secondary Objectives</strong></u> <ul> <li>To assess and compare progression-free survival (PFS) between arms.</li> <li>To assess and compare locoregional failure and distant metastasis between arms.</li> <li>To assess acute and late toxicity (CTCAE v5.0).</li> <li>To assess patient-reported outcomes quality of life (PRO/QOL), as measured by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) (primary PRO), between arms.</li> < (text too long for field)...