Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC

Study Overview
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Brief Summary
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Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing rapidly in the developed world. This has been attributed to a rise in Human Papillomavirus (HPV) infection. HPV+OPSCC is considered a distinct disease entity, affecting younger patients and has a good prognosis following treatment. Subsequently, patients can live with the considerable side effects for several decades. Radiotherapy and cetuximab (Epidermal Growth Factor Receptor-inhibitor) have demonstrated similar efficacy to 'platin' chemoradiotherapy (current standard treatment containing platinum-based compounds) in head and neck cancer, but is potentially less toxic. Results of this trial will be used to determine the optimum treatment of this debilitating cancer, with the primary aim of decreasing toxicity and improving quality of life for HPV+OPSCC patients.

Official Title
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Determination of Epidermal Growth Factor Receptor-inhibitor (Cetuximab) Versus Standard Chemotherapy (Cisplatin) Early And Late Toxicity Events in Human Papillomavirus-positive Oropharyngeal Squamous Cell Carcinoma

Conditions
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Oropharyngeal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cisplatin<br>Three doses of cisplatin 100mg/m2 given at days 1, 22 and 43 from start of radiotherapy. | Drug: Cisplatin<br> <br> |
| Experimental: Cetuximab<br>Initial dose of 400mg/m2 one week before start of radiotherapy followed by seven weekly doses of 250 mg/m2 during radiotherapy. | Drug: Cetuximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy. |  | Up to two years after end of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall number of events of acute severe toxicity between treatment arms. |  | Up to and including three months after end of treatment. | 
| Overall number of events of late severe toxicity between treatment arms. |  | From three months up to two years after end of treatment. | 
| Quality of life outcomes assessed by EORTC QLQ C30 and HN35 between the two treatment arms. |  | Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment. | 
| Effect on swallowing of the two treatment arms (assessed by MDADI and by PEG or RIG utilisation rate at 1 and 2 years). |  | Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment. | 
| Cost-effectiveness of the two treatment arms (assessed by EuroQoL-5D). | Questionnaires completed at the following time points: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment. | Up to two years after end of treatment. | 
| Overall survival and recurrence between the two arms. |  | Up to two years after end of treatment. |