Olaparib and Radiotherapy in Head and Neck Cancer

Exclusion Criteria

• •Patients eligible for concurrent chemoradiotherapy rather than radiotherapy alone
• •Concurrent active malignancy other than localized, non-melanoma skin cancer or carcinoma-in-situ of the cervix (unless definitive treatment was completed 3 years or more before study entry and the patient has remained disease free)
• •Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 3 weeks prior to start of therapy (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea). Patients may continue the use of LHRH agonists for cancer; bisphosphonates for bone disease and corticosteroids.
• •Major surgery within two weeks of starting study treatment.
• •Participation in other trial with investigational drug or treatment modality
• •Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication.
• •Tube feeding before the start of treatment.
• •Prior radiotherapy to head \& neck region.
• •Blood transfusion in the four weeks prior to study entry
• •Persistent toxicities (CTC ≥ grade 2) with the exception of alopecia, caused by previous cancer therapy
• •QT-interval \>470 msec
• •Significant cardiovascular disease as defined by:
• •* History of congestive heart failure defined as NYHA class III
• •* History of unstable angina pectoris or myocardial infarction up to 3 months prior to trial entry;
• •* Presence of severe valvular heart disease
• •* Presence of a ventricular arrhythmia requiring treatment;
• •* Uncontrolled hypertension
• •Patients considered a poor medical risk due to:
• •* non-malignant systemic disease
• •* active, uncontrolled infection requiring parenteral antibiotics
• •* a serious, uncontrolled medical disorder; examples include, but are not limited to:
• •* uncontrolled major seizure disorder
• •* unstable spinal cord compression
• •* superior vena cava syndrome
• •* extensive bilateral lung disease on HRCT scan
• •* any psychiatric disorder that prohibits obtaining informed consent.
• •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• •Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
• •Patients with known active hepatic disease (i.e. Hepatitis B or C)
• •Patients with myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear.
• •Concomitant medications:
• •* Any previous treatment with a PARP inhibitor, including olaparib
• •* Patients receiving the following classes of inhibitors of CYP3A4 (see paragraph 6.4.2 for guidelines and wash out periods)
• •* Azole antifungals
• •* Macrolide antibiotics
• •* Protease inhibitors
• •Breast-feeding women