E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell carcinoma of the head and neck (SCCHN) |
|
E.1.1.1 | Medical condition in easily understood language |
Squamous cell carcinoma of the head and neck (SCCHN) |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 general objectives are to evaluate the pre-operative activity and the safety of afatinib in head and neck cancer and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms.
The primary objective is to evaluate the pre operative activity of afatinib as assessed by Fluorodeoxyglucose – Positron emission tomography/Computed tomography (FDG-PET/CT). |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Newly diagnosed histologically proven squamous cell carcinoma of the
oral cavity, oropharynx, hypopharynx or larynx.
- Patients selected for a primary surgical treatment
- Performance status ECOG 0-1
Within 2 weeks prior to randomization:
- Adequate bone marrow function
- Adequate hepatic function times ULN
- Adequate renal function as demonstrated by serum creatinine
- Controlled blood pressure
- Adequate cardiac function
- FDG PET/CT
- DCE MRI and DWI MRI performed
- Primary tumor ≥2 cm in their largest diameter measured bidimensionally by imaging done within 2 weeks prior to randomization
- Availability of tumor and normal mucosa biopsies during staging endoscopy (please refer to surgical guidelines for further information).
- Availability of blood samples for Translational research
- Age ≥18 years
- Negative pregnancy test
- Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations |
|
E.4 | Principal exclusion criteria |
- Patients with nasopharynx, nasal cavity and paranasal sinuses carcinomas, or recurrent / metastatic SCCHN
- T3 -T4 hypopharyngeal SCCHN
- No distant metastases
- Active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix
- Prior chemotherapy, radiotherapy or targeted therapy including HER inhibitors (monoclonal antibodies or tyrosine kinase inhibitors) for
SCCHN
- No concomitant use of Potent P-gp inhibitors, Potent P-gp inducers, Erythropoietin (EPO)
- No evidence of diabetes
- No evidence of interstitial lung disease
- No weight loss of more than 10% in the previous 6 months
- Serious underlying medical conditions which could
impair the ability of the patient to participate in the study
- Participation in another interventional clinical trial in the preceding 30 days prior to randomization |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Metabolic response after 2 weeks of treatment and prior to surgery, assessed by Fluorodeoxyglucose – Positron emission tomography/ Computed tomography (FDG-PET/CT) according to EORTC guidelines for response published by Young et al 1999. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 2 weeks of treatment and prior to surgery |
|
E.5.2 | Secondary end point(s) |
- Imaging
- Surgical safety
- Translational research |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Imaging:
After 2 weeks of treatment and prior to surgery.
- Surgical safety:
Up to 4 weeks after surgery.
- Translational Research:
Undefined
|
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care (surgery only) |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | No |
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
|
End of study occurs when all of the following criteria have been satisfied:
1. Four weeks after all patients have had surgery.
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 15 |