E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cancers harbouring an EGFR mutation (excluding non-squamous non- small cell lung cancer, a registered indication), a HER2 mutation or a HER3 mutation |
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E.1.1.1 | Medical condition in easily understood language |
cancers harbouring an EGFR mutation (excluding non-squamous non- small cell lung cancer, a registered indication), a HER2 mutation or a HER3 mutation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 evaluate the objective response rate (CR+PR), using RECIST 1.1 criteria, of afatinib in cancers harbouring either an EGFR mutation, a HER2 mutation or a HER3 mutation, excluding EGFR mutated NSCLC and providing that there is no other tumour-specific genotype-based trial in Belgium for which the patient is eligible. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate disease control (CR+PR+SD) determined by RECIST
- To evaluate Progression Free Survival (PFS) and overall survival (OS)
- To evaluate safety by reporting all adverse events (AE) and grading using CTCAE criteria version 4.0 (33)
- To correlate tumor response with findings on tumor biopsies, analyzed by immunohistochemistry (if relevant) and mutational analysis.
- To investigate resistance mechanisms by performing a re-biopsy at progression
- To evaluate response rate determined by RECIST 1.1 and PFS on the combination therapy of afatinib and paclitaxel
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Women and men with locally advanced or metastatic cancers harboring either an activating EGFR mutation or a HER2 mutation or a HER3 mutation
• Failure of at least one line of standard systemic therapy
• No eligibility for other open genomic driven phase I, II or III trial available for these tumor genotypes
• ECOG performance status ≤2
• Patient with a life expectancy >3 months
• Patients able to provide written informed consent prior to enrollment into the clinical trial.
• Adequate organ function
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E.4 | Principal exclusion criteria |
• Non squamous non-small cell lung cancer harbouring an EGFR mutation (registered indication)
• Chemotherapy, biological therapy or investigational agents within four weeks prior to the start of study treatment
• Known hypersensitivity to afatinib or the excipients of any of the trial drugs
• Prior treatment with afatinib
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this trial is objective response (CR+PR) according to RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour assessment will be performed by CT or MRI of the chest and abdomen at baseline, every 8 weeks until cycle 7 and every 12 weeks thereafter |
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E.5.2 | Secondary end point(s) |
- Disease control rate (CR+PR+SD) according to RECIST 1.1 (34)
- PFS defined as the time from treatment start until documented tumor progression or death of any cause, whichever occurs first
- OS, defined as time from randomization until death (irrespective of reason).
- Safety of afatinib as indicated by incidence and intensity of AEs graded according to CTCAE v4.0 (33)
- To correlate tumor response with findings on tumor biopsies, analyzed by immunohistochemistry (if relevant) and mutational analysis
- To investigate resistance mechanisms by performing a re-biopsy at progression
- To evaluate response rate determined by RECIST 1.1 and PFS on the combination therapy of afatinib and paclitaxel
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumour assessment will be performed by CT or MRI of the chest and abdomen at baseline, every 8 weeks until cycle 7 and every 12 weeks thereafter |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
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
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |