Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC (De-ESCALaTE)

Inclusion Criteria:

• American Joint Committee on Cancer (AJCC) TNM Stage III-IVa (T3N0-T4N0, and T1N1-T4N3) oropharyngeal squamous cell carcinoma (SCC) tumours
• Clinical multidisciplinary team decision to treat with primary curative cisplatin chemoradiotherapy
• No previous treatment including surgery, except node biopsies or diagnostic tonsillectomy
• Medically fit (ECOG 0, 1 or 2)
• Adequate cardiovascular, haematological, renal and hepatic function
• Age > 18 years
• Written informed consent given
• Using adequate contraception [male and female participants]. Must take contraceptive measures during, and for at least six months after treatment.

Exclusion Criteria:

• Distant metastasis (i.e. AJCC TNM stage IVc disease)
• AJCC TNM Stage T1-2N0 disease
• Treated with primary radical surgery to the primary site (e.g. resection)
• Concurrent use of CYP3A4 inducers or inhibitors. [A standard course of dexamethasone or aprepitant for the prevention of cisplatin-induced nausea and vomiting is permitted]
• Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab [no history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities; no uncontrolled seizure disorder; no active neurologic disease; no neuropathy greater than grade 1]
• Patients who have p16+ tumours who also have N2b, N2c or N3 nodal disease and whose lifetime smoking history is also more than 10 pack years (i.e. have both risk factors).
• Pregnant or lactating
• Previous treatment for any other cancer with cytotoxics, radiotherapy or anti-EGFR therapies
• Inadequate renal, haematological or liver functions [Absolute neutrophil count <1,500/mm3; platelet count <100,000/mm3; WBC <3,000/mm3; haemoglobin <9 g/dL. [Haemoglobin correction by transfusion permitted.] Bilirubin > 1.5 times upper limit of normal (ULN); alkaline phosphatase > 2.5 times ULN; AST and ALT > 2.5 times ULN. Creatinine > 1.5 mg/dL; Creatinine clearance < 60 mL/min]
• Patients with clinically significant hearing impairment
• Life expectancy less than 3 months
• Other malignancy within the past 3 years except basal cell skin cancer or pre-invasive carcinoma of the cervix.