Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC

Oropharyngeal Squamous Cell Carcinoma Clinical Trial

— De-ESCALaTE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01874171
• Other study ID #: RMRCT0034
• Secondary ID: 2011-005165-21IS
• Status: Active, not recruiting
• Phase: Phase 3
• First received: June 6, 2013
• Last updated: May 4, 2017
• Start date: November 15, 2012
• Est. completion date: February 2019

Study information

• Verified date: May 2017
• Source: University of Warwick
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 334
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Oropharyngeal Squamous Cell Carcinoma

Intervention

Drug:
• Cisplatin

• Cetuximab

Locations

Country	Name	City	State
Ireland	Beaumont Hospital	Dublin
Ireland	St Luke's Hospital	Dublin
Netherlands	VU University Medical Center	Amsterdam
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Royal United Hospital	Bath
United Kingdom	Clatterbridge Cancer Centre	Bebington
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Bristol Haematology & Oncology Centre	Bristol
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	Colchester General Hospital	Colchester
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	University Hospitals Coventry & Warwickshire	Coventry
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Queen Elizabeth Hospital Birmingham	Edgbaston
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon & Exeter Hospital	Exeter
United Kingdom	Royal Surrey County Hospital	Guildford
United Kingdom	St James's Institute of Oncology	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Royal Marsden Hospital	London
United Kingdom	University College Hospital	London
United Kingdom	James Cook University Hospital	Middlesbrough
United Kingdom	New Cross Hospital	New Cross
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Norfolk & Norwich University Hospital	Norwich
United Kingdom	Nottingham University Hopsital	Nottingham
United Kingdom	Glan Clwyd Hospital	Rhyl
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury
United Kingdom	Royal Marsden Hospital	Sutton
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Musgrove Park Hospital	Taunton

Sponsors (4)

Lead Sponsor	Collaborator
University of Warwick	Cancer Research UK, University of Birmingham, University of Oxford

Countries where clinical trial is conducted

Ireland,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy.		Up to two years after end of treatment.
Secondary	Overall number of events of acute severe toxicity between treatment arms.		Up to and including three months after end of treatment.
Secondary	Overall number of events of late severe toxicity between treatment arms.		From three months up to two years after end of treatment.
Secondary	Quality of life outcomes assessed by EORTC QLQ C30 and HN35 between the two treatment arms.		Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Secondary	Effect on swallowing of the two treatment arms (assessed by MDADI and by PEG or RIG utilisation rate at 1 and 2 years).		Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Secondary	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.	Up to two years after end of treatment.
Secondary	Overall survival and recurrence between the two arms.		Up to two years after end of treatment.

External Links

•   De-ESCALaTE study website