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)

NCT01950689 | Completed Phase 3 DMC

• 1 other identifier: CFTSp032, 11_DOG08_53
• Study Type: interventional
• Target: 338
• Locations: 1 country
• Sites: 21

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Overall survival (enriched sub-group)

  Date of death for patient, month 60.

• Cancer-specific survival (enriched sub-group)

  follow up month 60

• Disease-free survival (enriched sub-group)

  follow up month 60

• Cumulative incidence of loco-regional failure

  follow up month 60

• Acute toxicity (all patients)

  baseline, week 1, 2, 3, 4, 5, 6, follow up month 1.5 and 3

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo given in parallel with radiotherapy for 6 weeks.

Radiation: Radiotherapy

Nimorazole

EXPERIMENTAL

Nimorazole given in parallel with radiotherapy for 6 weeks

Drug: Nimorazole; Radiation: Radiotherapy

Interventions

Nimorazole DRUG

Nimorazole

Radiotherapy RADIATION

Nimorazole; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead

Study Sites (21)

Cheltenham General Hospital

Cheltenham, Gloucestershire, GL53 7AN, United Kingdom

Location

Clatterbridge Centre for Oncology

Bebington, Merseyside, CH63 4JY, United Kingdom

Location

St James' Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Bradford Teaching Hospitals NHS Foundation Trust

Bradford, BD9 6RJ, United Kingdom

Location

Bristol Haematology and Oncology centre

Bristol, BS2 8ED, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

University Hospitals Coventry and Warwickshire

Coventry, CV2 2DX, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

The Royal Marsden

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The James Cook University Hospital

Middlesbrough, TS4 3BW, United Kingdom

Location

Nottingham University Hospitals

Nottingham, NG5 1PB, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

York Hospital

York, Y031 8HE, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Nimorazole; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• David Thomson

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Trials Manager

Study Record Dates

• First Submitted: September 23, 2013
• First Posted: September 25, 2013
• Study Start: September 11, 2014
• Primary Completion: January 7, 2021
• Study Completion: January 7, 2021
• Last Updated: October 19, 2021

Record last verified: 2021-10

Locations

GB (21)