Clinical trial NCT01950689: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
First posted: 2013-09-25
Enrollment: 338
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Locoregional Control in patients with more hypoxic tumours (the enriched population)
timeFrame: 12 weeks post treatment
Secondary outcomes:
measure: Overall survival (enriched sub-group)
timeFrame: Date of death for patient, month 60.
measure: Cancer-specific survival (enriched sub-group)
timeFrame: follow up month 60
measure: Disease-free survival (enriched sub-group)
timeFrame: follow up month 60
measure: Cumulative incidence of loco-regional failure
timeFrame: follow up month 60
measure: Acute toxicity (all patients)
timeFrame: baseline, week 1, 2, 3, 4, 5, 6, follow up month 1.5 and 3
measure: Hypoxia signature prediction of nimorazole benefit (all patients)
timeFrame: screening
measure: Quality of life (enriched sub-group)
timeFrame: baseline, week 6, month 6, 12, 18, 24, 36 of follow up
measure: Late toxicity (all patients)
timeFrame: baseline, follow up month 6, 12, 18, 24, 36
Other outcomes:
Locations:
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: Gloucestershire
city: Bebington
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: Merseyside
city: Leeds
country: United Kingdom
facility: St James' Hospital
state: West Yorkshire
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospitals NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology centre
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: Guildford
country: United Kingdom
facility: The Royal Surrey County Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: The Royal Marsden
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Middlesborough
country: United Kingdom
facility: The James Cook University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: York
country: United Kingdom
facility: York Hospital
Study officials:
affiliation: The Christie NHS Foundation Trust
name: David Thomson
role: PRINCIPAL_INVESTIGATOR
References: