NIMRAD (A Randomised Placebo-controlled Trial of Synchronous NIMorazole Versus RADiotherapy Alone in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Not Suitable for Synchronous Chemotherapy or Cetuximab)

Inclusion criteria

• Histologically confirmed (newly diagnosed/ not recurrent) head and neck squamous cell carcinoma; all primary subsites EXCEPT nasal cavity, oral cavity, nasopharynx and paranasal sinus (i.e. oropharynx, hypopharynx, larynx are allowed)
• Stage T3/T4 N0; any node +ve case including T1 node +ve; T2N0 base of tongue/hypopharynx
• Patients suitable for definitive radiotherapy. Block dissections may be performed pre-RT for N2/N3 disease
• WHO status 0-2
• Patient fit and able to undergo RT with nimorazole and be expected to complete treatment
• Absence of another disease or previous malignancy which is likely to interfere with the treatment or assessment of response
• No evidence of distant metastases (M0)
• Unable to tolerate/unlikely to benefit from platinum chemotherapy or monoclonal antibody therapy
• Women must be postmenopausal (no menstrual period for a minimum of 1 year) or have a negative serum pregnancy test on entry in the study (even if surgically sterilised) and be using an adequate contraception method. This must be continued for 1 week after completion of nimorazole, unless child bearing potential has been terminated by surgery/radical radiotherapy
• Men must be willing to use an adequate method of contraception during treatment and until 1 week after nimorazole
• Greater than 18 years of age; no upper age limit
• Available for follow up within the United Kingdom
• Adequate renal and liver function - absolute neutrophil count >=1.5 x 109/L, creatinine <=2x ULN, platelets > 100x109/L, total bilirubin <=2 x ULN, AST or ALT <3 x ULN
• The capacity to understand the patient information sheet and the ability to provide written informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion criteria

• Patients with T1N0 tumours or those within the nasopharynx, nasal cavity or sinus, oral cavity; T2No larynx and tonsil; unknown primary cancer.
• Any prior chemotherapy in the last 6 months or RT within the planned radiation field
• Presence of any life threatening illness such as unstable angina or severe chronic obstructive pulmonary disease
• Mental disability or patient otherwise unable to give informed consent and/or complete patient questionnaires
• Hb <100 g/l (patients with anaemia may be transfused to bring Hb levels to >100 g/l within 1 week of treatment start. Please repeat Hb following transfusion to confirm now eligible)
• Peripheral neurophathy as assessed clinically (CTCAE >=2)
• Use of any investigational drug within 30 days prior to screening
• Severe and/or uncontrolled medical disease
• Any malabsorption syndrome (i.e. partial gastrectomy, small bowel resection, Crohn's disease or ulcerative colitis)
• Use of Lithium or Phenobarbitone during the study
• Patients who are breastfeeding or pregnant
• Previous malignancy within 5 years (except BCC, in-situ Ca e.g. of the cervix)
• Previous definitive surgery to primary site