E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non Squamous Non Small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029520 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029520 |
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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 |
Assess the antitumor activity of pemetrexed in combination with cisplatin, as measured by Overall Response Rate after preoperative chemotherapy, in patients with stage IIIAN2 nonsquamous NSCLC |
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E.2.2 | Secondary objectives of the trial |
- Assess pathological complete remission rate after surgery, median progression-free survival (PFS), and median overall survival (OS) - Assess tumor downstaging - Characterize quantitative and qualitative toxicities - Assess the expression of biomarkers of interest and their correlation with Overall Response Rate - Assess the expression of biomarkers and their correlation with PFS and OS - Compare baseline expression of biomarkers with the expression of the same biomarkers after 3 cycles of pemetrexed/cisplatin chemotherapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Histologic diagnosis of NSCLC defined as other than predominantly squamous cell histology (squamous cell and/or mixed small cell, non-small cell histology is not permitted). [2] Stage IIIAN2 disease (T1aN2, T1bN2, T2aN2, T2bN2, and T3N2) (except pancoast tumors and bronchoalveolar carcinoma) as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer. [3] Tumor considered potentially resectable with no evidence of extrathoracic metastatic disease. [4] ECOG PS of 0 or 1. [5] No prior surgery, radiotherapy, systemic chemotherapy, immunotherapy, targeted, or biological therapy for NSCLC. [6] At least 1 unidimensionally measurable lesion meeting RECIST criteria version 1.1 (at least 10 mm in longest diameter [LD] by CT scan [slice thickness 5mm], or at least 20 mm LD by chest X-ray). For malignant lymph nodes, at least 15 mm in short axis when assessed by CT scan (slice thickness 5 mm). PET scans and ultrasounds may not be used for tumor measurements. [7] Estimated life expectancy of at least 6 months [8] Patient compliance and geographic proximity that allow adequate follow-up. [9] Adequate organ function including the following: Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) > or =1.5 x 109/L, platelets > or =100 x 109/L, and hemoglobin > or = 9 g/dL. Hepatic: bilirubin < or = 1.5 times the upper limit of normal (x ULN), alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) < or = 3.0 x ULN. Renal: calculated creatinine clearance (CrCl) > or = 45 mL/min based on the original weight-based Cockroft and Gault formula and serum creatinine < or = 1.5 x ULN. [10] Patients must sign an informed consent document (ICD). [11] Patients must be at least 18 years of age. [12] For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device, birth control pills, or barrier device) during and for 6 months after last dose of study drug; must have a negative serum or urine pregnancy test within 7 days before study enrollment; and must not be breast-feeding. For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 6 months after last dose of study drug. [13] Patients must have an adequate tumor tissue sample available for detection of biomarkers expression. [14] Predicted postresection forced expiratory volume in 1 second (FEV1) > or =1.2 L. [15] Patients must be fit for surgery at time on enrollment. |
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E.4 | Principal exclusion criteria |
[16] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [17] Have previously completed or withdrawn from this study or any other study investigating pemetrexed. [18] Have a serious concomitant systemic disorder (for example, active infection including human immunodeficiency virus) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. [19] Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV. [20] Have had a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score < or =6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously. [21] Are receiving concurrent administration of any other antitumor therapy. [22] Have received a recent (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination. [23] Are unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose < or = 1.3 grams per day. [24] Are unable or unwilling to take folic acid, vitamin B12 supplementation, or corticosteroids. [25] Have had significant (>5%) weight loss within 6 months of enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response rate defined as the proportion of patients whose response is Complete Response or Partial Response |
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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 | Yes |
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 | No |
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 | 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 | 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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Ultima visita dell`ultimo soggetto inserito nella sperimentazione |
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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 |