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

ISRCTN	ISRCTN33522080
DOI	https://doi.org/10.1186/ISRCTN33522080
EudraCT/CTIS number	2011-005165-21
ClinicalTrials.gov number	NCT01874171
Secondary identifying numbers	11723

Submission date: 20/02/2012
Registration date: 20/02/2012
Last edited: 29/10/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/cancer-help/trials/a-trial-looking-side-effects-treatment-throat-cancer-de-escalate-hpv

Study website

Contact information

Mrs Tessa Fulton-Lieuw
Scientific

Warwick Clinical Trials Unit
Division of Health Sciences
Warwick Medical School
The University of Warwick
Coventry
CV4 7AL
United Kingdom

Phone	+44 2476 574 880
Email	M.T.Fulton-Lieuw@warwick.ac.uk

Study information

Study design	Both; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	De-ESCALaTE HPV
Study objectives	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(s)	NRES Committee West Midlands Coventry & Warwickshire, 29/11/2011, ref: 11/WM/0381
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Cetuximab, cisplatin
Primary outcome measure	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 study start date	01/09/2011
Completion date	31/07/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	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.
Total final enrolment	334
Key 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]
Key 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
Date of first enrolment	09/10/2012
Date of final enrolment	28/10/2016

Locations

Countries of recruitment

Belgium
England
Ireland
Italy
Netherlands
Scotland
United Kingdom
Wales

Study participating centres

Warwick Clinical Trials Unit

University of Warwick
Coventry
CV4 7AL
United Kingdom

Aberdeen Royal Infirmary

Foresterhill Road
Aberdeen
AB25 2ZN
United Kingdom

St Luke’s Centre for Radiation at Beaumont Hospital

Beaumont Road
Dublin
-
Ireland

Bradford Royal Infirmary

BIHR – Temple Bank House
Bradford Royal Infirmary
Bradford
BD9 6RJ
United Kingdom

Bristol Haematology & Oncology Centre

Horfield Road
Bristol
BS2 8ED
United Kingdom

Castle Hill Hospital

Castle Road
Cottingham
HU16 5JQ
United Kingdom

Cheltenham General Hospital

Sandford Road
Cheltenham
GL53 7AN
United Kingdom

Clatterbridge Cancer Centre

Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom

Colchester General Hospital

Turner Road
Colchester
Essex
CO4 5JL
Colchester
CO4 5JL
United Kingdom

Glan Clwyd Hospital

North Wales Cancer Treatment Centre
Glan Clwyd Hospital
Bodelwyddan
Denbighshire
Bodelwyddan
LL18 5UJ
United Kingdom

James Cook University Hospital

Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Leicester Royal Infirmary

Infirmary Square
Leicester
LE1 5WW
United Kingdom

Musgrove Park Hospital

The Beacon Centre
Taunton
TA1 5DA
United Kingdom

New Cross Hospital

Deansley Centre
WV10 9PQ
United Kingdom

Nottingham City Hospital

Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Queen Elizabeth Hospital Birmingham

Cancer Centre, Edgbaston
Birmingham
B15 2TH
United Kingdom

Royal Derby Hospital

Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Royal Marsden Hospital (London)

Fulham Road
London
SW3 6JJ
United Kingdom

Royal Marsden Hospital (Sutton)

Downs Road
Sutton
Surrey
Sutton
SM2 5PT
United Kingdom

Royal Surrey County Hospital

Egerton Road
Guildford
GU2 7XX
United Kingdom

Royal United Hospital

Combe Park
Bath
BA1 3NG
United Kingdom

Singleton Hospital

Sketty Lane
Swansea
SA2 8QA
United Kingdom

St James's Institute of Oncology

Beckett Street
Leeds
LS9 7TF
United Kingdom

St Luke’s Hospital

Highfield Road
Rathgar
Dublin 6
Dublin
-
Ireland

University Hospitals Coventry & Warwickshire

Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Velindre Hospital

Whitchurch
Cardiff
CF14 2TL
United Kingdom

VU University Medical Center

De Boelelaan 1117
1081 HV
Netherlands

Manor Hospital

Moat Road
Walsall
WS2 9PS
United Kingdom

Western General Hospital

Crewe Road
Edinburgh
EH4 2XU
United Kingdom

Weston Park Hospital

Whitham Road
Sheffield
S10 2SJ
United Kingdom

Northampton General Hospital

Cliftonville
Northampton
NN1 5BD
United Kingdom

Norfolk & Norwich University Hospital

Colney Lane
Norwich
NR4 7UY
United Kingdom

Sponsor information

University of Warwick (UK)
University/education

Warwick Medical School
Medical School Building
Coventry
CV4 7AL
England
United Kingdom

"ROR"	https://ror.org/01a77tt86

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	31/12/2019
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	05/01/2019		Yes	No
Plain English results		06/02/2019	29/10/2021	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

29/10/2021: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.
20/11/2018: Publication reference added.
20/01/2017: Overall trial dates were updated from 01/03/2012 - 28/02/2015 to 01/09/2011 - 31/07/2019. Recruitment dates were updated from 01/03/2012 - 28/02/2015 to 09/10/2012 - 28/10/2016. Added trial participation centres.
17/01/2017: No publications found in PubMed, verifying study status with principal investigator.