Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC (De-ESCALaTE)

May 4, 2017 updated by: Prof. Janet Dunn, University of Warwick

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

334

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ireland
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland, 6
        • St Luke's Hospital
  • Netherlands
      • Amsterdam, Netherlands
        • VU University Medical Center
  • United Kingdom
      • Aberdeen, United Kingdom
        • Aberdeen Royal Infirmary
      • Bath, United Kingdom, BA1 3NG
        • Royal United Hospital
      • Bebington, United Kingdom, CH63 4JY
        • Clatterbridge Cancer Centre
      • Bradford, United Kingdom
        • Bradford Royal Infirmary
      • Bristol, United Kingdom, BS2 8ED
        • Bristol Haematology & Oncology Centre
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Hospital
      • Cheltenham, United Kingdom, GL53 7AN
        • Cheltenham General Hospital
      • Colchester, United Kingdom
        • Colchester General Hospital
      • Cottingham, United Kingdom
        • Castle Hill Hospital
      • Coventry, United Kingdom, CV2 2DX
        • University Hospitals Coventry & Warwickshire
      • Derby, United Kingdom
        • Royal Derby Hospital
      • Edgbaston, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital Birmingham
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital
      • Exeter, United Kingdom, EX2 5DW
        • Royal Devon & Exeter Hospital
      • Guildford, United Kingdom, GU2 7XX
        • Royal Surrey County Hospital
      • Leeds, United Kingdom, LS9 7TF
        • St James's Institute of Oncology
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
      • London, United Kingdom, NW1 2PG
        • University College Hospital
      • Middlesbrough, United Kingdom, TS4 3BW
        • James Cook University Hospital
      • New Cross, United Kingdom
        • New Cross Hospital
      • Northampton, United Kingdom
        • Northampton General Hospital
      • Norwich, United Kingdom
        • Norfolk & Norwich University Hospital
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham University Hopsital
      • Rhyl, United Kingdom
        • Glan Clwyd Hospital
      • Sheffield, United Kingdom, S10 2SJ
        • Weston Park Hospital
      • Shrewsbury, United Kingdom
        • Royal Shrewsbury Hospital
      • Sutton, United Kingdom
        • Royal Marsden Hospital
      • Swansea, United Kingdom, SA2 8QA
        • Singleton Hospital
      • Taunton, United Kingdom
        • Musgrove Park Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cisplatin
Three doses of cisplatin 100mg/m2 given at days 1, 22 and 43 from start of radiotherapy.
Drug: Cisplatin
Experimental: Cetuximab
Initial dose of 400mg/m2 one week before start of radiotherapy followed by seven weekly doses of 250 mg/m2 during radiotherapy.
Drug: Cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Up to two years after end of treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall number of events of acute severe toxicity between treatment arms.
Time Frame: Up to and including three months after end of treatment.
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.
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.
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.
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.
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.
Overall survival and recurrence between the two arms.
Time Frame: Up to two years after end of treatment.
Up to two years after end of treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Warwick

Collaborators

University of Oxford
Cancer Research UK
University of Birmingham

Investigators

  • Study Chair: Hisham Mehanna, PhD, BMedSc (hons), FRCS, University of Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2012

Primary Completion (Anticipated)

February 1, 2019

Study Completion (Anticipated)

February 1, 2019

Study Registration Dates

First Submitted

June 6, 2013

First Submitted That Met QC Criteria

June 6, 2013

First Posted (Estimate)

June 10, 2013

Study Record Updates

Last Update Posted (Actual)

May 8, 2017

Last Update Submitted That Met QC Criteria

May 4, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMRCT0034
  • 2011-005165-21 (EudraCT Number)
  • ISRCTN33522080 (Other Identifier: ISRCTN)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Oropharyngeal Squamous Cell Carcinoma

Clinical Trials on Cetuximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe