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

Primary Purpose

Oropharyngeal Squamous Cell Carcinoma

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cisplatin
Cetuximab
Sponsored by
University of Warwick
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oropharyngeal Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St Luke's Hospital
  • Beaumont Hospital
  • VU University Medical Center
  • Aberdeen Royal Infirmary
  • Royal United Hospital
  • Clatterbridge Cancer Centre
  • Bradford Royal Infirmary
  • Bristol Haematology & Oncology Centre
  • Velindre Hospital
  • Cheltenham General Hospital
  • Colchester General Hospital
  • Castle Hill Hospital
  • University Hospitals Coventry & Warwickshire
  • Royal Derby Hospital
  • Queen Elizabeth Hospital Birmingham
  • Western General Hospital
  • Royal Devon & Exeter Hospital
  • Royal Surrey County Hospital
  • St James's Institute of Oncology
  • Leicester Royal Infirmary
  • University College Hospital
  • Royal Marsden Hospital
  • James Cook University Hospital
  • New Cross Hospital
  • Northampton General Hospital
  • Norfolk & Norwich University Hospital
  • Nottingham University Hopsital
  • Glan Clwyd Hospital
  • Weston Park Hospital
  • Royal Shrewsbury Hospital
  • Royal Marsden Hospital
  • Singleton Hospital
  • Musgrove Park Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Cisplatin

Cetuximab

Arm Description

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

Initial dose of 400mg/m2 one week before start of radiotherapy followed by seven weekly doses of 250 mg/m2 during radiotherapy.

Outcomes

Primary Outcome Measures

Compare severe (acute and late) toxicity (Grade 3-5) caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy.

Secondary Outcome Measures

Overall number of events of acute severe toxicity between treatment arms.
Overall number of events of late severe toxicity between treatment arms.
Quality of life outcomes assessed by EORTC QLQ C30 and HN35 between the two treatment arms.
Effect on swallowing of the two treatment arms (assessed by MDADI and by PEG or RIG utilisation rate at 1 and 2 years).
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.
Overall survival and recurrence between the two arms.

Full Information

First Posted
June 6, 2013
Last Updated
May 4, 2017
Sponsor
University of Warwick
Collaborators
Cancer Research UK, University of Birmingham, University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT01874171
Brief Title
Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Unknown status
Study Start Date
November 15, 2012 (Actual)
Primary Completion Date
February 2019 (Anticipated)
Study Completion Date
February 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Warwick
Collaborators
Cancer Research UK, University of Birmingham, University of Oxford

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
334 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cisplatin
Arm Type
Active Comparator
Arm Description
Three doses of cisplatin 100mg/m2 given at days 1, 22 and 43 from start of radiotherapy.
Arm Title
Cetuximab
Arm Type
Experimental
Arm Description
Initial dose of 400mg/m2 one week before start of radiotherapy followed by seven weekly doses of 250 mg/m2 during radiotherapy.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
Overall number of events of acute severe toxicity between treatment arms.
Time Frame
Up to and including three months after end of treatment.
Title
Overall number of events of late severe toxicity between treatment arms.
Time Frame
From three months up to two years after end of treatment.
Title
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.
Title
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.
Title
Cost-effectiveness of the two treatment arms (assessed by EuroQoL-5D).
Description
Questionnaires completed at the following time points: Baseline, end of treatment, and 3, 6, 12 & 24 months after end of treatment.
Time Frame
Up to two years after end of treatment.
Title
Overall survival and recurrence between the two arms.
Time Frame
Up to two years after end of treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hisham Mehanna, PhD, BMedSc (hons), FRCS
Organizational Affiliation
University of Birmingham
Official's Role
Study Chair
Facility Information:
Facility Name
St Luke's Hospital
City
Dublin
ZIP/Postal Code
6
Country
Ireland
Facility Name
Beaumont Hospital
City
Dublin
Country
Ireland
Facility Name
VU University Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
Country
United Kingdom
Facility Name
Royal United Hospital
City
Bath
ZIP/Postal Code
BA1 3NG
Country
United Kingdom
Facility Name
Clatterbridge Cancer Centre
City
Bebington
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
Bradford Royal Infirmary
City
Bradford
Country
United Kingdom
Facility Name
Bristol Haematology & Oncology Centre
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
Facility Name
Velindre Hospital
City
Cardiff
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Facility Name
Cheltenham General Hospital
City
Cheltenham
ZIP/Postal Code
GL53 7AN
Country
United Kingdom
Facility Name
Colchester General Hospital
City
Colchester
Country
United Kingdom
Facility Name
Castle Hill Hospital
City
Cottingham
Country
United Kingdom
Facility Name
University Hospitals Coventry & Warwickshire
City
Coventry
ZIP/Postal Code
CV2 2DX
Country
United Kingdom
Facility Name
Royal Derby Hospital
City
Derby
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital Birmingham
City
Edgbaston
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Facility Name
Royal Devon & Exeter Hospital
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Royal Surrey County Hospital
City
Guildford
ZIP/Postal Code
GU2 7XX
Country
United Kingdom
Facility Name
St James's Institute of Oncology
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
University College Hospital
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
James Cook University Hospital
City
Middlesbrough
ZIP/Postal Code
TS4 3BW
Country
United Kingdom
Facility Name
New Cross Hospital
City
New Cross
Country
United Kingdom
Facility Name
Northampton General Hospital
City
Northampton
Country
United Kingdom
Facility Name
Norfolk & Norwich University Hospital
City
Norwich
Country
United Kingdom
Facility Name
Nottingham University Hopsital
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Glan Clwyd Hospital
City
Rhyl
Country
United Kingdom
Facility Name
Weston Park Hospital
City
Sheffield
ZIP/Postal Code
S10 2SJ
Country
United Kingdom
Facility Name
Royal Shrewsbury Hospital
City
Shrewsbury
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
Sutton
Country
United Kingdom
Facility Name
Singleton Hospital
City
Swansea
ZIP/Postal Code
SA2 8QA
Country
United Kingdom
Facility Name
Musgrove Park Hospital
City
Taunton
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://www.warwick.ac.uk/go/deescalate
Description
De-ESCALaTE study website

Learn more about this trial

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

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