A randomised multicentre accelerated radiotherapy study of dose escalated intensity modulated radiotherapy versus standard dose intensity modulated radiotherapy in patients receiving treatment for locally advanced laryngeal and hypopharyngeal cancers
To determine the potential of dose escalated intensity modulated radiotherapy (IMRT) to improve locoregional failure free rate (LRFFR) and laryngeal preservation in patients with locally advanced laryngeal and hypopharyngeal cancers, without increasing the incidence of severe acute and late toxicities to unacceptable levels.
Central London Research Ethics Committee (REC) 4 approved on 18/10/2010 (ref: 10/H0715/48)
Parallel group phase III multicentre randomised controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Locally advanced squamous cell cancers of the larynx or hypopharynx
The dose escalated IMRT (experimental) treatment group will receive 67.2 Gy in 28 fractions (2.4 Gy per fraction) to the involved site and nodal groups and 56 Gy in 28 fractions (2.0 Gy per fraction) to nodal areas at risk of harbouring microscopic disease.
The standard dose IMRT (standard) treatment group will receive 65 Gy in 30 fractions (2.167 Gy per fraction) to the involved site and nodal groups and 54 Gy in 30 fractions (1.8 Gy per fraction) to nodal areas at risk of harbouring microscopic disease.
All patients will receive concomitant cisplatin 100 mg/m2 on day 1 and day 29 of the radiotherapy schedule however within the context of this trial, chemotherapy is not an investigational medicinal product.
Primary outcome measures
Locoregional failure free rate (LRFFR).
Measured at 1, 2, 3, 4 and 8 weeks post-treatment and at 3, 6, 12, 18 and 24 months post treatment. Patients will then be followed up annually up to 5 years.
Secondary outcome measures
1. Laryngo-oesophageal dysfunction free rate
2. Overall survival (time from randomisation to death)
3. Acute and late toxicities following chemoradiation
4. Characteristics of patients who proceed to salvage neck dissection
5. Characteristics of patients who fail organ preservation
All of the above will be measured at 1, 2, 3, 4 and 8 weeks post-treatment and at 3, 6, 12, 18 and 24 months post treatment. Patients will then be followed up annually up to 5 years.
6. Patient assessed quality of life, measured using questionnaires administered at baseline, end of radiotherpay treatment, 6 months, 1 year and then annually to 5 years post-treatment
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Aged 16 years or above, either sex
2. Histologically confirmed squamous cell cancer of the larynx or hypopharynx
3. Chemo-radiotherapy is the investigators treatment of choice. Induction chemotherapy is permitted.
4. Locally advanced squamous cell cancer of the larynx or hypopharynx i.e. stage III or IV a/b disease
5. World Health Organization (WHO) performance status of 0 or 1
6. Creatinine clearance of greater than 50 ml/min
7. Must be suitable to attend long term follow-up. All patients participating in the QoL study must have adequate cognitive ability to complete the QoL questionnaires.
8. Written informed consent
Patients may undergo surgical biopsy or non-radical surgery prior to study entry.
Target number of participants
Participant exclusion criteria
1. Previous radiotherapy to the head and neck region
2. Clinical evidence of metastatic disease (Stage IVc)
3. Previous malignancy except non-melanoma skin cancer and early stage cancer in remission for at least 5 years following treatment
4. Previous or concurrent illness, which in the investigator's opinion would interfere with completion of therapy
5. Pre-existing previous speech or swallowing problems unrelated to the diagnosis of cancer
6. Large primary tumour, where organ preservation is unrealistic
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Director Head and Neck Unit, Consultant Reader in Oncology
Royal Marsden NHS Foundation Trust (UK)
Cancer Research UK (CRUK) (UK) (ref: CRUK/10/018)
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting