NIMRAD (NIMorazole/placebo plus RADiotherapy in head and neck cancer)
Research type
Research Study
Full title
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.
IRAS ID
132094
Contact name
Nick Slevin
Contact email
Eudract number
2013-002466-39
Clinicaltrials.gov Identifier
Research summary
Summary of Research
Standard of care for locally-advanced head and neck squamous cell carcinoma (HNSCC) is radiotherapy plus concurrent cisplatin or concurrent cetuximab (if cisplatin cannot be tolerated). A third of locally-advanced HNSCC patients are aged >70 and due to tolerance and safety concerns, most will receive radiotherapy alone as standard treatment. A single randomised placebo-controlled trial (DAHANCA5) (1990s) showed that giving the radiosensitiser nimorazole with radiotherapy improves locoregional control with no increased toxicity. Since DAHANCA5, radiotherapy plus nimorazole is the standard of care in Denmark. Azanta recently adopted nimorazole, which has orphan drug status, to develop commercially. \nNIMRAD is a randomised, placebo controlled double-blind, multicentre UK study to assess if patients with locally-advanced HNSCC unsuitable for cisplatin chemotherapy or monoclonal antibody therapy benefit from improved locoregional control without additional serious toxicity. A total of 470 patients will receive treatment over a 4 year recruitment period.\nFollowing consent and successful screening, patients will be randomised to receive standard intensity-modulated radiotherapy (IMRT) plus nimorazole/placebo. The nimorazole/placebo tablets will be given 90 minutes before each radiotherapy fraction. Radiotherapy will be delivered to a total of 65 Gy in 30 fractions over 6 weeks (5 days per week). Patients will be seen weekly during radiotherapy, at 6 and 12 weeks post-radiotherapy, then at 6 months, 12 months, 6 monthly in year 2 and annually in years 3 to 5 for follow-up (with a minimum follow-up of 2 years). Toxicity and quality-of-life will be assessed throughout.\nGiven the evidence that hypoxic tumours benefit most from hypoxia modification, a separate translational study will aim to identify patients who are most likely to benefit from this hypoxia intervention, and for this patients will be asked to consent to donating archival tissue and a fresh blood sample at baseline for future radiogenomic researchSummary of Results
Head and neck cancers with low levels of oxygen are more difficult to treat with radiotherapy than cancers with a normal oxygen level. Nimorazole is a drug that gets into the cancer cells with a low level of oxygen. These cancers may then be more effectively treated by radiotherapy.
Patients with head and neck cancer who were unable to receive chemotherapy alongside radiotherapy (for example due to reduced fitness, medical problems, or older age), were randomised in one group to have radiotherapy and a placebo drug, and in the other group to have radiotherapy and nimorazole.
338 patients were recruited from 19 UK centres between May 2014 and May 2019. The average patient age was 73 years (range, 44-88); and clinical factors were balanced between the treatment groups. A sample of the cancer was tested using a gene signature to find out the tumour oxygen level.
In total, 3 out of 4 patients in the nimorazole group took the drug for more than half of the radiotherapy fractions. Nimorazole caused more nausea than placebo, with no differences in other early or late toxicities.
Nimorazole did not improve the effectiveness of radiotherapy to increase tumour control, or the chance of patient survival, in either the group of patients with cancers that had lower oxygen levels or in all patients.
.REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
13/EE/0397
Date of REC Opinion
24 Jan 2014
REC opinion
Further Information Favourable Opinion