E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 overall aim is to investigate whether immediate maintenance pemetrexed therapy prolongs survival compared to observation and pemetrexed therapy at progression in patients with advanced NSCLC. |
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E.2.2 | Secondary objectives of the trial |
Furthermore, we will explore whether patients with PS 2 and elderly ≥ 70 years tolerate and benefit from maintenance therapy; and what clinical characteristics and blood biomarkers are associated with sensitivity and tolerability of such therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. No prior systemic therapy for advanced non-small-cell lung cancer (including EGFR-TKI). Previous chemotherapy (e.g. adjuvant after surgery or for other cancer) is allowed if ≥ 3 months since the last course was administered. 2. Measureable disease according to the RECIST 1.1 3. Previous radiotherapy is acceptable provided there are measurable, previously not irradiated lesions present. 4. Histologically or cytologically confirmed non-squamous non-small cell lung cancer 5. No activating EGFR-mutation or ALK-translocation detected 6. Stage IIIB ineligible for curative therapy or stage IV disease 7. Age ≥ 18 years 8. ECOG Performance 0-2 9. Adequate organ function defined as: a. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy. b. Total serum bilirubin ≤ 1.5 x ULN c. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L d. Platelets ≥ 100 x 109/L e. Creatinin clearance > 45 ml/min 10. No serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) that in the opinion of the investigator would compromise the patient’s ability to complete the study or interfere with the evaluation of the efficacy and safety of the study treatment 11. No conditions – medical, social, psychological – which could prevent adequate information and follow-up 12. No clinical active cancer other than NSCLC 13. No known hypersensitivity or contraindications for the study drugs (vinorelbine, carboplatin, pemetrexed, B12, folate,) 14. Able to discontinue NSAIDs and ASA if reduced renal function 15. No pregnancy or lactating women 16. All fertile patients should use safe contraception 17. Written informed consent
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E.4 | Principal exclusion criteria |
See principal inclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuously evaluation during the study. Last follow-up 24 months after last patient included. |
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E.5.2 | Secondary end point(s) |
• Progression free survival • Toxicity • Health related quality of life
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation with CT-scan after 6 and 12 weeks after randomization, and thereafter every 9 week. Evaluation of toxicity during each treatment cycle. Evaluation of health related quality of life before every second treatment cycle |
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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 | No |
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 | No |
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 | 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 | 15 |
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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Progressive 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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |