Condition category
Cancer
Date applied
20/02/2012
Date assigned
20/02/2012
Last edited
11/11/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
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
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.

More details can be found at http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=11723

Ethics approval

NRES Committee West Midlands – Coventry & Warwickshire approved on 29 Nov 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

01/03/2012

Overall trial end date

28/02/2015

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

01/03/2012

Recruitment end date

28/02/2015

Locations

Countries of recruitment

Belgium, Italy, Netherlands, United Kingdom

Trial participating centre

Warwick Clinical Trials Unit
Coventry
CV4 7AL
United Kingdom

Sponsor information

Organisation

University of Warwick (UK)

Sponsor details

Warwick Medical School
Coventry
CV4 7AL
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

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

Publication summary

Publication citations

Additional files

Editorial Notes