E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population consists of patients aged 18 years and older who have histologicaly or cytologicaly proven locally advanced or metastatic NSCLC with activating mutation of EGFR, chemonaive and without prior treatment with TKIs who fullfill all eligibility criteria. Treatment Investigational treatment consists of 4 to 6 initial 3-weekly cycles of chemotherapy with gemcitabine-cisplatin and intermittent erlotinib, followed by maintenance treatment with erlotinib.
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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 objectives is response rate: proportion of patients in complete remission (CR), partial remission (PR), minimal response and stable disease (SD) and progression (Prog), assessed according to RECIST |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: •time to tumor progression (TTP) – clinical and/or radiologic progression according to RECIST •overall survival •metabolic response to treatment – comparison of PET-CT uptake before treatment, on day 140 – 160 and on day 360 – 380 after start of treatment •toxicity •quality of life.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the study, patients should meet the following criteria: •patient's understanding of the disease and treatment and signed written informed consent •age 18 years or older •histo-pathological or cytological diagnosis of non-small cell lung cancer of non-squamous type •positive for mutation of EGFR •disease stage IV (Stage IV a or IV b) and unsuitable for surgical treatment or for radiotherapy with curative intent •no history of other malignancy; or in complete remission for > 3 years if previously treated for other malignancy •chemo-naïve; or more than 3 years after chemotherapy for other cancer; or received not more than 1 cycle of chemotherapy for this cancer •no previous treatment with TKIs •if previously treated by radiotherapy, all acute radiation-related toxicity has resolved and the interval is > 2 weeks for total dose ≥ 30 Gy or > 10 days for total dose < 30 Gy •no clinical symptoms of brain metastases. Patients after surgery and/or radiotherapy for brain metastases and patients with asymptomatic small (< 2 cm) brain metastases are eligible if they meet other eligibility criteria •according to clinical presentation, no indication for radiotherapy is foreseen until eventual progression of the disease. An exception to this rule are patients with asymptomatic small brain metastases who may be treated with whole-brain radiotherapy in fractions not greater than 2.5 Gy during maintenance treatment with erlotinib (i.e. after completion of 4 cycles of gemcitabine/cisplatin + erlotinib) •measurable and previously unirradiated disease. Bone metastases as the only measurable lesions are not eligible •performance status ≥ 70% (Karnofsky); or ECOG 0 – 2 •hemoglobin > 100 g/L •neutrophils > 2.0 g/L •platelets > 100 x 109 /L •kidney function: creatinine within normal limits + ECC > 60 mL/min; or ECC > 100 mL/min •liver function: bilirubin < 1.25 x UNL; AST/ALT < 2 x UNL (in case of liver metastases AST/ALT < 5 x UNL) •cardiac compensation
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E.4 | Principal exclusion criteria |
Exclusion criteria •Stage IV a or IV b with solitary metastasis considered for surgery and/or radiotherapy with curative intent •peripheral neuropathy grade 2 or more (common toxicity criteria – CTC, NCI), unless mechanical in origin •vascular disease grade 2 or more (CTC) •active infection or other serious concomitant disease; •treatment with unapproved medicinal product within 30 days prior to start of study treatment •pregnancy, breastfeeding, or refusal of using acceptable methods of birth control throughout the study to prevent pregnancy.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objectives is response rate: proportion of patients in complete remission (CR), partial remission (PR), minimal response and stable disease (SD) and progression (Prog), assessed according to RECIST |
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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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 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 | Information not present in EudraCT |
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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Therapy will continue until progression of disease or unacceptable toxicity. |
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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 | 3 |
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 | 3 |
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 |