E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced 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 | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
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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 | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
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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 |
The primary objective of this study is to compare maintenance therapy with pemetrexed plus BSC versus placebo plus BSC, in terms of objective PFS time in patients with Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV nonsquamous NSCLC whose disease has not progressed during 4 cycles of pemetrexed + cisplatin induction chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are to compare the following between randomized treatment arms: Time-to-event efficacy endpoint: o OS Objective tumor response rate Patient-reported outcomes using the EuroQol 5-dimensional scale (EQ 5D) Resource utilization Toxicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1)Histological or cytological 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 IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or Stage IV prior to induction therapy, as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer, that is not amenable to curative therapy (see Protocol Attachment S124.2; Fleming et al. 1997). [3] ECOG performance status (PS) of 0 or 1 (Oken et al. 1982) (see Protocol Attachment S124.3). [4] Patients must have had no prior systemic chemotherapy for lung cancer. [5] Previous radiation therapy is allowed to <25% of the bone marrow (Cristy and Eckerman 1987), but should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study enrollment. Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy. [6] At least 1 unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST; see Protocol Attachment S124.4) criteria (at least 10 mm in longest diameter by spiral computerized tomography [CT] scan, or at least 20 mm by standard techniques). Positron emission tomography (PET) scans and ultrasounds may not be used for tumor measurements. [7] Estimated life expectancy of at least 12 weeks. [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) 1.5  109/L, platelets 100  109/L, and hemoglobin 9 g/dL. Hepatic: bilirubin 1.5 times the upper limit of normal ( ULN); alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) 3.0  ULN (AP, AST, and ALT 5  ULN is acceptable if liver has tumor involvement). Renal: calculated creatinine clearance (CrCl)  mL/min based on the original weight based Cockcroft and Gault formula (see Protocol Attachment S124.5; Cockcroft and Gault 1976). [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 highly reliable contraceptive method (failure rate <1%) during and for 6 months after the treatment period; 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 the treatment period. |
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E.4 | Principal exclusion criteria |
(13) Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [14] Have previously completed or withdrawn from this study or any other study investigating pemetrexed. [15] Have a serious concomitant systemic disorder (for example, active infection including human immunodeficiency virus) that, in the opinion of the investigator, would compromise the patients ability to adhere to the protocol. [16] 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 (see Protocol Attachment S124.6). [17] 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 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously. [18] Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening CT scan or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required. [19] Are receiving concurrent administration of any other antitumor therapy. [20] Have clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry. [21] Have received a recent (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination. [22] Have received prior systemic anticancer therapy for lung cancer (including adjuvant early-stage treatment for NSCLC). [23] Are unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). [24] Are unable or unwilling to take folic acid, vitamin B12 supplementation, or corticosteroids. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome of the study is the PFS.Objective Progression-Free Survival Time is defined as the time from the date of randomization to the first of date of objectively determined progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free disease assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study drug) prior to objectively determined disease progression or death, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation chemotherapy. |
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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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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Lo studio terminera' nel 2011, approssimativamente 9 mesi dopo che l'ultimo paziente verra' randomizzato nella fase di mantenimento. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | |
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 |