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)

The Christie NHS Foundation Trust

Status and phase: Completed; Phase 3

Conditions: Head and Neck Squamous Cell Carcinoma

Treatments: Drug: Nimorazole; Radiation: Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01950689

CFTSp032, 11_DOG08_53

Details and patient eligibility

About

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.

Enrollment: 338 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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338 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo given in parallel with radiotherapy for 6 weeks.

Treatment:

Radiation: Radiotherapy

Nimorazole

Experimental group

Description:

Nimorazole given in parallel with radiotherapy for 6 weeks

Treatment:

Drug: Nimorazole

Radiation: Radiotherapy