Condition category
Cancer
Date applied
20/02/2012
Date assigned
20/02/2012
Last edited
26/01/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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

Sponsor information

Organisation

University of Warwick (UK)

Sponsor details

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

Sponsor type

University/education

Website

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

Publication citations

Additional files

Editorial Notes

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.