Oropharyngeal Squamous Cell CarcinomaPhase 3De-ESCALaTENCT01874171
Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC
A Phase 3 study testing Cisplatin and Cetuximab in people with Oropharyngeal Squamous Cell Carcinoma, run by University of Warwick at 33 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oropharyngeal Squamous Cell Carcinoma
- What is being tested?
- Cisplatin and Cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 334 participants
- Where
- 33 sitesin 3 countries
- Study dates
- 15 Nov 2012to Feb 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- American Joint Committee on Cancer (AJCC) TNM Stage III-IVa (T3N0-T4N0, and T1N1-T4N3) oropharyngeal squamous cell carcinoma (SCC) tumours
- Clinical multidisciplinary team decision to treat with primary curative cisplatin chemoradiotherapy
- No previous treatment including surgery, except node biopsies or diagnostic tonsillectomy
- Medically fit (ECOG 0, 1 or 2)
- Adequate cardiovascular, haematological, renal and hepatic function
- Age > 18 years
- Written informed consent given
- Using adequate contraception [male and female participants]. Must take contraceptive measures during, and for at least six months after treatment.
Who cannot join
- Distant metastasis (i.e. AJCC TNM stage IVc disease)
- AJCC TNM Stage T1-2N0 disease
- Treated with primary radical surgery to the primary site (e.g. resection)
- Concurrent use of CYP3A4 inducers or inhibitors. [A standard course of dexamethasone or aprepitant for the prevention of cisplatin-induced nausea and vomiting is permitted]
- Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab [no history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities; no uncontrolled seizure disorder; no active neurologic disease; no neuropathy greater than grade 1]
- Patients who have p16+ tumours who also have N2b, N2c or N3 nodal disease and whose lifetime smoking history is also more than 10 pack years (i.e. have both risk factors).
Show all 12Show fewer
- Pregnant or lactating
- Previous treatment for any other cancer with cytotoxics, radiotherapy or anti-EGFR therapies
- Inadequate renal, haematological or liver functions [Absolute neutrophil count <1,500/mm3; platelet count <100,000/mm3; WBC <3,000/mm3; haemoglobin <9 g/dL. [Haemoglobin correction by transfusion permitted.] Bilirubin > 1.5 times upper limit of normal (ULN); alkaline phosphatase > 2.5 times ULN; AST and ALT > 2.5 times ULN. Creatinine > 1.5 mg/dL; Creatinine clearance < 60 mL/min]
- Patients with clinically significant hearing impairment
- Life expectancy less than 3 months
- Other malignancy within the past 3 years except basal cell skin cancer or pre-invasive carcinoma of the cervix.
Trial locations and contacts
33 sites in 3 countries.
33 sites in 3 countries
United Kingdom30 sites
Aberdeen Royal Infirmary
Aberdeen
Royal United Hospital
Bath, BA1 3NG
Clatterbridge Cancer Centre
Bebington, CH63 4JY
Bradford Royal Infirmary
Bradford
Bristol Haematology & Oncology Centre
Bristol, BS2 8ED
Velindre Hospital
Cardiff, CF14 2TL
Cheltenham General Hospital
Cheltenham, GL53 7AN
Colchester General Hospital
Colchester
Castle Hill Hospital
Cottingham
University Hospitals Coventry & Warwickshire
Coventry, CV2 2DX
Royal Derby Hospital
Derby
Queen Elizabeth Hospital Birmingham
Edgbaston, B15 2TH
Western General Hospital
Edinburgh, EH4 2XU
Royal Devon & Exeter Hospital
Exeter, EX2 5DW
Royal Surrey County Hospital
Guildford, GU2 7XX
St James's Institute of Oncology
Leeds, LS9 7TF
Leicester Royal Infirmary
Leicester, LE1 5WW
University College Hospital
London, NW1 2PG
Royal Marsden Hospital
London, SW3 6JJ
James Cook University Hospital
Middlesbrough, TS4 3BW
New Cross Hospital
New Cross
Northampton General Hospital
Northampton
Norfolk & Norwich University Hospital
Norwich
Nottingham University Hopsital
Nottingham, NG5 1PB
Glan Clwyd Hospital
Rhyl
Weston Park Hospital
Sheffield, S10 2SJ
Royal Shrewsbury Hospital
Shrewsbury
Royal Marsden Hospital
Sutton
Singleton Hospital
Swansea, SA2 8QA
Musgrove Park Hospital
Taunton
About this study
Official title: 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
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 (Epidermal Growth Factor Receptor-inhibitor) have demonstrated similar efficacy to 'platin' chemoradiotherapy (current standard treatment containing platinum-based compounds) 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.
- Conditions
- Oropharyngeal Squamous Cell Carcinoma
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cisplatin | Active comparator | Three doses of cisplatin 100mg/m2 given at days 1, 22 and 43 from start of radiotherapy. Receives: Drug: Cisplatin |
| Cetuximab | Experimental | Initial dose of 400mg/m2 one week before start of radiotherapy followed by seven weekly doses of 250 mg/m2 during radiotherapy. Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy.
Measured: Up to two years after end of treatment.
Secondary outcomes (6)
Overall number of events of acute severe toxicity between treatment arms.
Measured: Up to and including three months after end of treatment.
Overall number of events of late severe toxicity between treatment arms.
Measured: From three months up to two years after end of treatment.
Quality of life outcomes assessed by EORTC QLQ C30 and HN35 between the two treatment arms.
Measured: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Effect on swallowing of the two treatment arms (assessed by MDADI and by PEG or RIG utilisation rate at 1 and 2 years).
Measured: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Cost-effectiveness of the two treatment arms (assessed by EuroQoL-5D).
Questionnaires completed at the following time points: Baseline, end of treatment, and 3, 6, 12 \& 24 months after end of treatment.
Measured: Up to two years after end of treatment.
Overall survival and recurrence between the two arms.
Measured: Up to two years after end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2013 (estimated)
- Study start15 Nov 2012
- Primary completionFeb 2019 (estimated)
- Study completionFeb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oropharyngeal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 334 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Warwick
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, University of Birmingham, University of Oxford
- Responsible party
- Principal investigator, Prof. Janet Dunn, University of Warwick
- Investigators
- Hisham Mehanna, PhD, BMedSc (hons), FRCS, Study chair, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01874171
- Sponsor's protocol ID
- RMRCT0034
- Other IDs
- 2011-005165-21, ISRCTN33522080
- Acronym
- De-ESCALaTE
- Status last verified
- May 2017
- First submitted
- 6 Jun 2013
- Last updated
- 8 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01874171
- Acronym / sponsor ID
- De-ESCALaTE / RMRCT0034
- Conditions
- Oropharyngeal Squamous Cell Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 334 participants (actual)
- Lead sponsor
- University of WarwickUniversity, hospital or other
- Collaborators
- Cancer Research UK, University of Birmingham, University of Oxford
- Study start
- 15 Nov 2012 (actual)
- Primary completion
- Feb 2019 (estimated)
- Study completion
- Feb 2019 (estimated)
- First posted
- 10 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (Epidermal Growth Factor Receptor-inhibitor) have demonstrated similar efficacy to 'platin' chemoradiotherapy (current standard treatment containing platinum-based compounds) 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cisplatin | Active comparator | Drug: CisplatinThree doses of cisplatin 100mg/m2 given at days 1, 22 and 43 from start of radiotherapy. |
| Cetuximab | Experimental | Drug: CetuximabInitial dose of 400mg/m2 one week before start of radiotherapy followed by seven weekly doses of 250 mg/m2 during radiotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- American Joint Committee on Cancer (AJCC) TNM Stage III-IVa (T3N0-T4N0, and T1N1-T4N3) oropharyngeal squamous cell carcinoma (SCC) tumours
- Clinical multidisciplinary team decision to treat with primary curative cisplatin chemoradiotherapy
- No previous treatment including surgery, except node biopsies or diagnostic tonsillectomy
- Medically fit (ECOG 0, 1 or 2)
- Adequate cardiovascular, haematological, renal and hepatic function
Key exclusion criteria (12 listed)
- Distant metastasis (i.e. AJCC TNM stage IVc disease)
- AJCC TNM Stage T1-2N0 disease
- Treated with primary radical surgery to the primary site (e.g. resection)
- Concurrent use of CYP3A4 inducers or inhibitors. [A standard course of dexamethasone or aprepitant for the prevention of cisplatin-induced nausea and vomiting is permitted]
- Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab [no history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities; no uncontrolled seizure disorder; no active neurologic disease; no neuropathy greater than grade 1]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cisplatin | Drug | Cisplatin |
| Cetuximab | Drug | Cetuximab |
Primary outcome
Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy.
Time frame: Up to two years after end of treatment.
6 secondary outcomes
Overall number of events of acute severe toxicity between treatment arms.
Time frame: Up to and including three months after end of treatment.
Overall number of events of late severe toxicity between treatment arms.
Time frame: From three months up to two years after end of treatment.
Quality of life outcomes assessed by EORTC QLQ C30 and HN35 between the two treatment arms.
Time frame: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Effect on swallowing of the two treatment arms (assessed by MDADI and by PEG or RIG utilisation rate at 1 and 2 years).
Time frame: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Cost-effectiveness of the two treatment arms (assessed by EuroQoL-5D).
Time frame: Up to two years after end of treatment.
Overall survival and recurrence between the two arms.
Time frame: Up to two years after end of treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- De-ESCALaTE study websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hisham Mehanna, PhD, BMedSc (hons), FRCS study chair
University of Birmingham
33 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cisplatin and Cetuximab in people with Oropharyngeal Squamous Cell Carcinoma, run by University of Warwick at 33 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United Kingdom, Ireland, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy. (time frame: Up to two years after end of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2017.