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)

Phase 3

Completed

• Conditions: Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: Nimorazole; Radiation: Radiotherapy

• Registration Number: NCT01950689
• Lead Sponsor: The Christie NHS Foundation Trust

Brief Summary

The purpose of this study is to see whether adding Nimorazole to standard radiotherapy benefits patients with locally advanced head and neck squamous cell carcinoma.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-09-23
• Study First Submitted QC: 2013-09-23
• Study First Posted: 2013-09-25
• Study Start: 2014-09-11
• Primary Completion: 2021-01-07
• Study Completion: 2021-01-07
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-11
• Last Update Posted: 2021-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 338

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nimorazole	Nimorazole	Nimorazole given in parallel with radiotherapy for 6 weeks
Placebo	Radiotherapy	Placebo given in parallel with radiotherapy for 6 weeks.
Nimorazole	Radiotherapy	Nimorazole given in parallel with radiotherapy for 6 weeks

Primary Outcome Measures

Name	Time	Method
Locoregional Control in patients with more hypoxic tumours (the enriched population)	12 weeks post treatment	To examine whether patients with locally advanced head and neck squamous cell carcinoma unsuitable for either cisplatin chemotherapy or monoclonal antibody therapy benefit from the addition of nimorazole to standard definitive radiotherapy in terms of increased locoregional control without additional serious toxicity.

Secondary Outcome Measures

Name	Time	Method
Overall survival (enriched sub-group)	Date of death for patient, month 60.
Disease-free survival (enriched sub-group)	follow up month 60
Cancer-specific survival (enriched sub-group)	follow up month 60
Late toxicity (all patients)	baseline, follow up month 6, 12, 18, 24, 36
Acute toxicity (all patients)	baseline, week 1, 2, 3, 4, 5, 6, follow up month 1.5 and 3
Hypoxia signature prediction of nimorazole benefit (all patients)	screening
Cumulative incidence of loco-regional failure	follow up month 60
Quality of life (enriched sub-group)	baseline, week 6, month 6, 12, 18, 24, 36 of follow up

Trial Locations

Locations (21)

Belfast City Hospital; 🇬🇧 Belfast, United Kingdom

Weston Park Hospital; 🇬🇧 Sheffield, United Kingdom

Cheltenham General Hospital; 🇬🇧 Cheltenham, Gloucestershire, United Kingdom

Bradford Teaching Hospitals NHS Foundation Trust; 🇬🇧 Bradford, United Kingdom

Queen Elizabeth Hospital; 🇬🇧 Birmingham, United Kingdom

Nottingham University Hospitals; 🇬🇧 Nottingham, United Kingdom

The James Cook University Hospital; 🇬🇧 Middlesborough, United Kingdom

York Hospital; 🇬🇧 York, United Kingdom

St James' Hospital; 🇬🇧 Leeds, West Yorkshire, United Kingdom

Clatterbridge Centre for Oncology; 🇬🇧 Bebington, Merseyside, United Kingdom

Bristol Haematology and Oncology centre; 🇬🇧 Bristol, United Kingdom

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

Velindre Cancer Centre; 🇬🇧 Cardiff, United Kingdom

University Hospitals Coventry and Warwickshire; 🇬🇧 Coventry, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

The Royal Surrey County Hospital; 🇬🇧 Guildford, United Kingdom

University College London Hospital; 🇬🇧 London, United Kingdom

The Royal Marsden; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

The Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Singleton Hospital; 🇬🇧 Swansea, United Kingdom