Contact information
Type
Scientific
Primary contact
Mrs Tessa Fulton-Lieuw
ORCID ID
Contact details
Warwick Clinical Trials Unit
Division of Health Sciences
Warwick Medical School
The University of Warwick
Coventry
CV4 7AL
United Kingdom
+44 2476 574 880
M.T.Fulton-Lieuw@warwick.ac.uk
Additional identifiers
EudraCT number
2011-005165-21
ClinicalTrials.gov number
NCT01874171
Protocol/serial number
11723
Study information
Scientific title
De-ESCALaTE HPV: Determination of Epidermal growth factor receptor-inhibitor (cetuximab) versus Standard Chemotherapy (cisplatin) early And Late Toxicity Events in Human Papillomavirus-positive oropharyngeal squamous cell carcinoma: a randomised controlled trial
Acronym
De-ESCALaTE HPV
Study hypothesis
Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing rapidly in the developed world. This has been attributed to a rise in Human Papillomavirus (HPV) infection. HPV+ OPSCC is considered a distinct disease entity, affecting younger patients and has a good prognosis following treatment. Subsequently, patients can live with the considerable side effects for several decades.
Radiotherapy and cetuximab have demonstrated similar efficacy to platin chemoradiotherapy in head and neck cancer, but is potentially less toxic.
Results of this trial will be used to determine the optimum treatment of this debilitating cancer, with the primary aim of decreasing toxicity and improving quality of life for HPV+OPSCC patients.
Ethics approval
NRES Committee West Midlands Coventry & Warwickshire, 29/11/2011, ref: 11/WM/0381
Study design
Both; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Head and Neck Cancer; Disease: Head and Neck
Intervention
HPV positive patients will be randomised to receive either cisplatin + radiotherapy (Arm A) or cetuximab + radiotherapy (Arm B) and will be followed up for two years. Patients that are HPV negative will enter into the Registration Cohort Study.
Cetuximab, Initial dose of 400mg/m2, administered intravenously, 1 week before start of radiotherapy followed by 7 weekly doses of 250mg/m2, administered intravenously. during radiotherapy.
Cisplatin, Three doses of cisplatin 100mg/m2, administered intravenously, on days 1, 22 and 43 of radiotherapy.
Intervention type
Drug
Phase
Phase III
Drug names
Cetuximab, cisplatin
Primary outcome measures
Current primary outcome as of 13/03/2012:
Severe toxicity (acute and late) (Grade 3-5); Timepoint(s): Two years from end of treatment
Previous primary outcome:
Severe toxicity (Grade 3-5); Timepoint(s): Two years from end of treatment
Secondary outcome measures
1. Acute severe toxicity; Timepoint(s): 3 months from end of treatment
2. Late severe toxicity; Timepoint(s): Two years from end of treatment
3. Quality of Life; Timepoint(s): Two years from end of treatment
4. Dysphagia; Timepoint(s): Two years from end of treatment
5. Cost effectiveness; Timepoint(s): Two years from end of treatment
6. Overall survival, recurrence and metastasis; Timepoint(s): Two years from end of treatment
Overall trial start date
01/09/2011
Overall trial end date
31/07/2019
Reason abandoned
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 13/03/2012:
1. Stage III-IVa oropharyngeal squamous cell tumours
2. Clinical multidisciplinary team decision to treat with primary curative chemoradiotherapy
3. No previous treatment for the primary tumour, including surgery, neck dissection or tracheostomy [except node biopsies or diagnostic tonsillectomy]
4. Medically fit Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
5. Adequate cardiovascular, haematological, renal and hepatic function
6. Age 18 years or over
7. Written informed consent given
8. Using adequate contraception [male and female participants]. Must take contraceptive measures during, and for at least three months after treatment.
Previous inclusion criteria:
1. Stage III-IVa oropharyngeal squamous cell tumours
2. Clinical multidisciplinary team decision to treat with primary curative chemoradiotherapy
3. No previous treatment for the primary tumour, including surgery, neck dissection or tracheostomy [except node biopsies or diagnostic tonsillectomy]
4. Medically fit Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
5. Adequate cardiovascular, haematological, renal and hepatic function
6. Age 18 years or over
7. Written informed consent given
8. Using adequate contraception [male and female participants]
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 304; UK Sample Size: 304; Description: Depending on the number of participants recruited by international sites, the UK sample size may be smaller.
Participant exclusion criteria
Current exclusion criteria as of 13/03/2012:
1. Distant metastasis (i.e. stage IVc disease)
2. Tumor, Node, Metastasis (TNM) Stage T1-2N0 disease
3. Treated with primary radical surgery to the primary site e.g. resection
4. Concurrent use of CYP3A4 inducers or inhibitors
5. Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab
6. HPV+ patients who have p16+ tumours who also have N2b, N2c or N3 nodal disease and who also smoke more than 10 pack years (i.e. have both risk factors)
7. Pregnant or lactating
8. Previous treatment for any other cancer with cytotoxics, radiotherapy or antiEGFR therapies
9. Inadequate renal, haematological or liver functions
10. Patients with clinically significant hearing impairment.
11. Life expectancy less than three months
12. Other malignancy within the past three years except basal cell skin cancer or preinvasive carcinoma of the cervix
Previous exclusion criteria:
1. Distant metastasis (i.e. stage IVc disease)
2. Tumor, Node, Metastasis (TNM) Stage T1-2N0 disease
3. Treated with primary radical surgery to the primary site e.g. resection
4. Concurrent use of CYP3A4 inducers or inhibitors
5. Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab
6. HPV+ patients who have p16+ tumours who also have N2b, N2c or N3 nodal disease and who also smoke more than 10 pack years (i.e. have both risk factors)
7. Pregnant or lactating
8. Previous treatment for any other cancer with cytotoxics, radiotherapy or antiEGFR therapies
9. Inadequate renal, haematological or liver functions
10. Life expectancy less than three months
11. Other malignancy within the past three years except basal cell skin cancer or preinvasive carcinoma of the cervix
Recruitment start date
09/10/2012
Recruitment end date
28/10/2016
Locations
Countries of recruitment
Belgium, Italy, Netherlands, United Kingdom
Trial participating centre
Warwick Clinical Trials Unit
University of Warwick
Coventry
CV4 7AL
United Kingdom
Trial participating centre
Aberdeen Royal Infirmary
Foresterhill Road
Aberdeen
AB25 2ZN
United Kingdom
Trial participating centre
St Luke’s Centre for Radiation at Beaumont Hospital
Beaumont Road
Dublin
-
Ireland
Trial participating centre
Bradford Royal Infirmary
BIHR – Temple Bank House
Bradford Royal Infirmary
Bradford
BD9 6RJ
United Kingdom
Trial participating centre
Bristol Haematology & Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Trial participating centre
Castle Hill Hospital
Castle Road
Cottingham
HU16 5JQ
United Kingdom
Trial participating centre
Cheltenham General Hospital
Sandford Road
Cheltenham
GL53 7AN
United Kingdom
Trial participating centre
Clatterbridge Cancer Centre
Clatterbridge Road
Bebington,
Wirral
CH63 4JY
United Kingdom
Trial participating centre
Colchester General Hospital
Turner Road
Colchester
Essex
CO4 5JL
Colchester
CO4 5JL
United Kingdom
Trial participating centre
Glan Clwyd Hospital
North Wales Cancer Treatment Centre
Glan Clwyd Hospital
Bodelwyddan
Denbighshire
Bodelwyddan
LL18 5UJ
United Kingdom
Trial participating centre
James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Trial participating centre
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Trial participating centre
Musgrove Park Hospital
The Beacon Centre
Taunton
TA1 5DA
United Kingdom
Trial participating centre
New Cross Hospital
Deansley Centre
WV10 9PQ
United Kingdom
Trial participating centre
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
Queen Elizabeth Hospital Birmingham
Cancer Centre, Edgbaston
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Trial participating centre
Royal Marsden Hospital (London)
Fulham Road
London
SW3 6JJ
United Kingdom
Trial participating centre
Royal Marsden Hospital (Sutton)
Downs Road
Sutton
Surrey
Sutton,
SM2 5PT
United Kingdom
Trial participating centre
Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom
Trial participating centre
Royal United Hospital
Combe Park
Bath
BA1 3NG
United Kingdom
Trial participating centre
Singleton Hospital
Sketty Lane
Swansea
SA2 8QA
United Kingdom
Trial participating centre
St James's Institute of Oncology
Beckett Street
Leeds
LS9 7TF
United Kingdom
Trial participating centre
St Luke’s Hospital
Highfield Road
Rathgar
Dublin 6,
Dublin
-
Ireland
Trial participating centre
University Hospitals Coventry & Warwickshire
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
Trial participating centre
Velindre Hospital
Whitchurch
Cardiff
CF14 2TL
United Kingdom
Trial participating centre
VU University Medical Center
De Boelelaan 1117
1081 HV
Netherlands
Trial participating centre
Manor Hospital
Moat Road
Walsall
WS2 9PS
United Kingdom
Trial participating centre
Western General Hospital
Crewe Road
Edinburgh
EH4 2XU
United Kingdom
Trial participating centre
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Trial participating centre
Northampton General Hospital
Cliftonville
Northampton
NN1 5BD
Trial participating centre
Norfolk & Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD Sharing Plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/12/2019
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary