Phase I Study of Olaparib Combined With Cisplatin-based Chemoradiotherapy to Treat Locally Advanced Head and Neck Cancer

Prior treatment

• Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
• Previous therapy with a PARP inhibitor
• Chemotherapy, immunotherapy or radiotherapy within 28 days prior to registration
• The current use of drugs which are known to inhibit or induce CYP3A4

Other illness

• Head \& neck cancers of the following types: Nasopharyngeal and paranasal sinus tumours, Oral squamous cell carcinomas (tumours of the oral cavity), Low risk Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
• Confirmed distant metastatic disease
• Prior history of malignancy, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate. Patient must have been free of malignancy for a period of 3 years prior to first dose of trial drug
• Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
• Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician's judgment, could interfere with patient safety or obtaining informed consent
• Known hepatitis B or C infection (testing for Hepatitis and HIV for the trial is not mandatory)
• Immunocompromised patients (e.g. known HIV positive status)
• Active uncontrolled infection
• Patients with myelodysplastic syndrome/acute myeloid leukaemia.
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.

Lab values

• Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.

Other

• Women who are pregnant or lactating
• Grade 3 or 4 peripheral neuropathy - If considered significant by the treating clinician a lower grade neuropathy may be considered as exclusion criterion
• Significant hearing difficulties or tinnitus (deaf patients can be included) - Whilst not excluded, patients with mildly impaired hearing or tinnitus must be made aware of potential ototoxicity and may choose not to be included. If included, it is recommended that audiograms be carried out at baseline.

• Histologically confirmed high-risk locally advanced HNSCC, patients who would normally be offered cisplatin-based radical chemoradiotherapy
• Estimated life expectancy of at least 16 weeks
• WHO performance status 0 or 1
• Aged ≥18 years
• Adequate bone marrow function: absolute neutrophils grade 0 or 1, platelets grade 0 or 1, haemoglobin grade 0 or 1
• Adequate renal function: Creatinine grade 0 or 1, Calculated GFR ≥60 mL/min (if calculated value is \<60 mL/min then an isotope GFR assessment should be performed or an estimation from 24h urine collection)
• Adequate liver function: Serum bilirubin grade 0 or 1, AST or ALT grade 0 or 1
• Patients must be able to swallow olaparib tablets
• Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
• Able to give informed consent
• Patients willing and able to comply with the protocol for the duration of the study