Weekly Cetuximab/RT Versus Weekly Cisplatin/RT in HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Inclusion Criteria:

1. Aged 18 years or older
2. Has provided written Informed Consent for participation in this trial
3. Histologically confirmed squamous cell carcinoma of the oropharynx with p16 positive status confirmed locally by immunohistochemistry
4. Stage III (excluding T1-2N1) or stage IV (excluding T4, N3, and distant metastasis) if smoking history of \< /=10 pack years. If \> 10 pack years nodal disease must be N0 - N2a.
5. If an excisional biopsy has been performed, patients remain eligible for the study provided there is clinically measurable disease prior to commencing RT. The residual disease should still meet the stage criteria required for the trial e.g. excisional biopsy of a node with residual T3 primary, or tonsillectomy for T1 primary with residual \> N2a nodes.
6. No prior treatment for oropharyngeal cancer
7. Adequate haematological, renal, and hepatic function as defined by,

   1. Absolute neutrophil count (ANC, segs + bands) \> /= 1.5 x 109/L
   2. Platelet count \> /= 100 x 109/L
   3. Total bilirubin \< /= 1.5 x upper normal limit
   4. ALT \< /= 2.5 x upper normal limit
   5. Calculated creatinine clearance (Cockcroft-Gault formula) or isotopic GFR \> 55ml/min
8. ECOG performance status score of 0-1
9. Participants capable of childbearing are using adequate contraception and intend to continue use of contraception for at least 6 months following completion of treatment
10. Negative pregnancy test within 72 hours prior to randomisation of women who are of childbearing potential
11. Suitable for follow-up for at least 24 months as per trial protocol.
12. Sufficient proficiency in English, cognitive capacity and willingness to complete questionnaires

Exclusion Criteria:

1. History of unknown primary of the head and neck
2. T4, N3 or distant metastases
3. Smoking history \>10 pack years with N2b or c nodal status
4. Women who are pregnant or lactating.
5. Previous radiotherapy to the area to be treated (excluding superficial radiotherapy for a cutaneous malignancy)
6. Previous cisplatin or carboplatin chemotherapy
7. Prior EGFR targeted therapy of any kind
8. Primary surgery to the affected area (excisional biopsy allowed)
9. Peripheral neuropathy \> /= grade 2 (CTCAE v4.0)
10. Sensori-neural hearing impairment \>= grade 2 (CTCAE v4.0, hearing impaired, not enrolled on a monitoring program) which may be exacerbated by cisplatin (Audiometric abnormalities without corresponding clinical deafness will not be grounds for exclusion)
11. Tinnitus \> /= grade 2 (CTCAE v4.0)
12. History of interstitial lung disease or evidence of interstitial lung disease on pre-registration CT
13. History of myocardial infarction within 12 months prior to study entry, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, uncontrolled psychotic disorders, active serious infections, active peptic ulcer disease, immunosuppression due to post-organ transplantation or use of immunosuppressants for autoimmune disorders
14. Patients known to be HIV positive
15. Other cancer that was diagnosed:

    1. more than 5 years prior to current diagnosis with (i) subsequent evidence of disease recurrence or (ii) clinical expectation of recurrence is greater than 10% or
    2. within 5 years of the current diagnosis, with the exception of successfully treated basal cell or squamous cell skin carcinoma, in situ melanoma, or carcinoma in situ of the cervix