E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Papillomavirus oropharyngeal squamous cell carcinoma. |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the throat associated with HPV. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057444 |
E.1.2 | Term | Oropharyngeal neoplasm |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary end point is evaluable 2 years after end of treatment for each patient. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are as follows:
● Compare overall number of events of acute severe toxicity (defined as occurring during treatment or within 90 days of end of treatment) between treatment arms, and also the overall number of serious adverse events. Compare overall number of events of late severe toxicity (defined as occurring more than 90 days up to two years from end 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 QoL 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 two arms.
● Report locoregional recurrence rates for both arms. |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject (LVLS). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |