Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck (ORCA)

Inclusion Criteria:

• Histologically confirmed high risk, locally advanced HNSCC patients (TNM staging: T-any N2/3 M0, bulky T3 or T4 N-any M0) who would normally be offered cisplatin-based radical chemoradiotherapy
• Estimated life expectancy of at least 12 weeks
• WHO performance status of 0 or 1
• Aged ≥18 years of age
• Adequate major organ function
• Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
• Able to give informed consent
• Willing and able to comply with the protocol for the duration of the study

Exclusion Criteria:

• Head & neck cancers of the following types:
• Nasopharyngeal and paranasal sinus tumours,
• Oral squamous cell carcinomas (tumours of the oral cavity),
• Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
• Confirmed distant metastatic disease
• Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
• Previous therapy with a PARP inhibitor
• Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
• Grade 3 or 4 peripheral neuropathy
• Significant hearing difficulties or tinnitus (deaf patients can be included)
• The current use of drugs which are known to inhibit or induce CYP3A4