Clinical trial NCT01874171: Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Oropharyngeal Squamous Cell Carcinoma
Lead sponsor: University of Warwick
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: University of Birmingham
name: University of Oxford
First posted: 2013-06-10
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy.
timeFrame: Up to two years after end of treatment.
Secondary outcomes:
measure: Overall number of events of acute severe toxicity between treatment arms.
timeFrame: Up to and including three months after end of treatment.
measure: Overall number of events of late severe toxicity between treatment arms.
timeFrame: From three months up to two years after end of treatment.
measure: Quality of life outcomes assessed by EORTC QLQ C30 and HN35 between the two treatment arms.
timeFrame: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
measure: Effect on swallowing of the two treatment arms (assessed by MDADI and by PEG or RIG utilisation rate at 1 and 2 years).
timeFrame: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
measure: Cost-effectiveness of the two treatment arms (assessed by EuroQoL-5D).
timeFrame: Up to two years after end of treatment.
measure: Overall survival and recurrence between the two arms.
timeFrame: Up to two years after end of treatment.
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St Luke's Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Bebington
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edgbaston
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Leeds
country: United Kingdom
facility: St James's Institute of Oncology
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: New Cross
country: United Kingdom
facility: New Cross Hospital
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hopsital
city: Rhyl
country: United Kingdom
facility: Glan Clwyd Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: University of Birmingham
name: Hisham Mehanna, PhD, BMedSc (hons), FRCS
role: STUDY_CHAIR
References: