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

NCT01874171 | Unknown Phase 3 DMC

• 3 other identifiers: RMRCT00342011-005165-21ISRCTN33522080
• Study Type: interventional
• Target: 334
• Locations: 3 countries
• Sites: 33

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.

Conditions

Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall number of events of acute severe toxicity between treatment arms.

  Up to and including three months after end of treatment.

• Overall number of events of late severe toxicity between treatment arms.

  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.

  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).

  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).

  Up to two years after end of treatment.

Study Arms (2)

Cisplatin

ACTIVE COMPARATOR

Three doses of cisplatin 100mg/m2 given at days 1, 22 and 43 from start of radiotherapy.

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.

Drug: Cetuximab

Interventions

Cisplatin DRUG

Cisplatin

Cetuximab DRUG

Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Warwick: lead
• Cancer Research UK: collaborator
• University of Birmingham: collaborator
• University of Oxford: collaborator

Study Sites (33)

St Luke's Hospital

Dublin, 6, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

Clatterbridge Cancer Centre

Bebington, CH63 4JY, United Kingdom

Location

Bradford Royal Infirmary

Bradford, United Kingdom

Location

Bristol Haematology & Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Velindre Hospital

Cardiff, CF14 2TL, United Kingdom

Location

Cheltenham General Hospital

Cheltenham, GL53 7AN, United Kingdom

Location

Colchester General Hospital

Colchester, United Kingdom

Location

Castle Hill Hospital

Cottingham, United Kingdom

Location

University Hospitals Coventry & Warwickshire

Coventry, CV2 2DX, United Kingdom

Location

Royal Derby Hospital

Derby, United Kingdom

Location

Queen Elizabeth Hospital Birmingham

Edgbaston, B15 2TH, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Royal Devon & Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

St James's Institute of Oncology

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

University College Hospital

London, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

James Cook University Hospital

Middlesbrough, TS4 3BW, United Kingdom

Location

New Cross Hospital

New Cross, United Kingdom

Location

Northampton General Hospital

Northampton, United Kingdom

Location

Norfolk & Norwich University Hospital

Norwich, United Kingdom

Location

Nottingham University Hopsital

Nottingham, NG5 1PB, United Kingdom

Location

Glan Clwyd Hospital

Rhyl, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Royal Shrewsbury Hospital

Shrewsbury, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

Musgrove Park Hospital

Taunton, United Kingdom

Location

Related Links

• De-ESCALaTE study website

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hisham Mehanna, PhD, BMedSc (hons), FRCS

  University of Birmingham

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Trials

Study Record Dates

• First Submitted: June 6, 2013
• First Posted: June 10, 2013
• Study Start: November 15, 2012
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: May 8, 2017

Record last verified: 2017-05

Locations

NL (1); IE (2); GB (30)