Human Papillomavirus oropharyngeal squamous cell carcinoma. MedDRA version: 19.0 Level: PT Classification code 10057444 Term: Oropharyngeal neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Cisplatin
Product Name: Cisplatin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Cisplatin
CAS Number: 82847-81-2
Concentration unit: mg/ml milligram(s)/millilitre
Concent
Sponsors
University of Warwick
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Stage III-IVa oropharyngeal squamous cell tumours. 2. Clinical multidisciplinary team decision to treat with primary curative chemoradiotherapy. 3. No previous treatment for the primary tumour, including surgery, neck dissection or tracheostomy [except node biopsies or diagnostic tonsillectomy]. 4. Medically fit (ECOG 0, 1 or 2). 5. Adequate cardiovascular, haematological, renal and hepatic function. 6. Age 18 years or over. 7. Written informed consent given. 8. Using adequate contraception [male and female participants]. Must take contraceptive measures during, and for at least six months after treatment. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: 1. Distant metastasis (i.e. stage IVc disease). 2. TNM Stage T1-2N0 disease. 3. Treated with primary radical surgery to the primary site e.g. resection. 4. Concurrent use of CYP3A4 inducers or inhibitors. 5. Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab. 6. HPV+ 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). 7. Pregnant or lactating. 8. Previous treatment for any other cancer with cytotoxics, radiotherapy or anti-EGFR therapies. 9. Inadequate renal, haematological or liver functions. 10. Patients with clinically significant hearing impairment. 11. Life expectancy less than three months. 12. Other malignancy within the past three years except basal cell skin cancer or pre-invasive carcinoma of the cervix.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the severe (acute and late) toxicity (Grade 3-5), as assessed by CTCAE Version 4, caused by cetuximab and radiotherapy to that caused by cisplatin and radiotherapy in patients with Human Papillomavirus related oropharyngeal squamous cell carcinoma (HPV+OPSCC).;Secondary Objective: The secondary objectives are as follows: To compare overall number of events of acute severe toxicity between treatment arms. To compare overall number of events of late severe toxicity between treatment arms. To compare the quality of life outcomes between the two treatment arms. To compare the effect on swallowing of the two treatment arms. To compare the cost-effectiveness of the two treatment arms. To report overall survival, recurrence and metastasis between the two arms.;Primary end point(s): The primary outcome measure will be the total number of acute and late severe or life-threatening (Grade 3-5) toxicity events occurring up to 2 years after treatment, and will be compared between both arms. This has been chosen as a primary end point because these important events have been shown to result in significant morbidity, with significant large impairments in overall quality of life of patients. ;Timepoint(s) of evaluation of this end point: The primary end point is evaluable 2 years after end of treatment for each patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary end points are as follows: • The number of acute severe (Grade 3-5) toxicities in cetuximab arm compared to cisplatin arm. Acute is defined as occurring during treatment or within 90 days of end of treatment. • The number of late severe (Grade 3-5) toxicities in cetuximab arm compared to cisplatin arm. Late is defined as overall number of toxicities occurring after 90 days of end of treatment up to 2 years after completion of treatment. • Global QoL using EORTC global measure in (a) acute phase (baseline to 6 months) and (b) late phase (baseline to 2 years). • EORTC swallowing quality of life domain at 1 and 2 years, swallowing function at 1 and 2 years measured by overall MDADI score, and PEG utilisation rates at 1 year and 2 years. • Comparison of incremental cost per quality-adjusted life year gained within trial and extrapolated over lifetime. • Report overall survival in 2 arms. • Report locoregional recurrence rates for both arms.;Timepoint(s) of evaluation of this end point: The timepoint is 2 years after end of treatment for each patient for all secondary end points except acute toxicity, which is 90 days after treatment. | — |
Countries
Ireland, Netherlands, United Kingdom
Contacts
Public ContactTessa Fulton-Lieuw
University of Warwick
Outcome results
None listed