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)

Head and Neck Squamous Cell Carcinoma Clinical Trial

— NIMRAD  

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01950689
• Other study ID #: CFTSp032, 11_DOG08_53
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2014
• Est. completion date: January 7, 2021

Study information

• Verified date: October 2021
• Source: The Christie NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: January 7, 2021
• Est. primary completion date: January 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Nimorazole

Radiation:
• Radiotherapy

Locations

Country	Name	City	State
United Kingdom	Clatterbridge Centre for Oncology	Bebington	Merseyside
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Bradford Teaching Hospitals NHS Foundation Trust	Bradford
United Kingdom	Bristol Haematology and Oncology centre	Bristol
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham	Gloucestershire
United Kingdom	University Hospitals Coventry and Warwickshire	Coventry
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	The Royal Surrey County Hospital	Guildford
United Kingdom	St James' Hospital	Leeds	West Yorkshire
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	The Royal Marsden	London
United Kingdom	University College London Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	The James Cook University Hospital	Middlesborough
United Kingdom	Nottingham University Hospitals	Nottingham
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Singleton Hospital	Swansea
United Kingdom	York Hospital	York

Sponsors (1)

Lead Sponsor	Collaborator
The Christie NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Locoregional Control in patients with more hypoxic tumours (the enriched population)	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.	12 weeks post treatment
Secondary	Overall survival (enriched sub-group)		Date of death for patient, month 60.
Secondary	Cancer-specific survival (enriched sub-group)		follow up month 60
Secondary	Disease-free survival (enriched sub-group)		follow up month 60
Secondary	Cumulative incidence of loco-regional failure		follow up month 60
Secondary	Acute toxicity (all patients)		baseline, week 1, 2, 3, 4, 5, 6, follow up month 1.5 and 3
Secondary	Hypoxia signature prediction of nimorazole benefit (all patients)		screening
Secondary	Quality of life (enriched sub-group)		baseline, week 6, month 6, 12, 18, 24, 36 of follow up
Secondary	Late toxicity (all patients)		baseline, follow up month 6, 12, 18, 24, 36