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 | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
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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 | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
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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 best supportive care (BSC) versus placebo plus BSC, in terms of objective progression-free survival (PFS) time in patients with Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV non squamous 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:overall survival time • Objective tumor response rate • Patient-reported outcomes using the EuroQol 5-dimensional scale • Resource utilization • Toxicity
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Translational Research Protocol Addendum - Protocol addendum(1) dated 11-Nov-2008. The primary objective of this TR study is to examine the association between the molecular marker TS and the objective progression-free survival (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. Other lung and pemetrexed biomarkers will be evaluated depending on sufficient tissue availability. |
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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 [3] ECOG performance status (PS) of 0 or 1 [4] Patients must have had no prior systemic chemotherapy for lung cancer. [5] Patients with prior radiation therapy may be eligible for this study if they meet the following guidelines: Previous radiation therapy is allowed to <25% of the bone marrow, 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 thoracic 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. Palliative extrathoracic radiotherapy to preexisting lesions may continue on study; however, these lesions may not be included as sites of measurable disease. [6] At least 1 unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST) criteria. 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) > 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 aminotransferase (AST), and alanine aminotransferase (ALT) < or = 3.0 x ULN (AP, AST, and ALT < or = 5 x ULN is acceptable if liver has tumor involvement). • Renal: calculated creatinine clearance (CrCl) > or = 45 mL/min based on the original weight based Cockcroft and Gault formula [10] Patients must sign an informed consent document [11] Patients must be at least 18 years of age [12] For women: Must be surgically sterile, post-menopausal, 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.
Related to the sub-study: [1] For collection of first (baseline) biopsy specimens: • Patients must have provided informed consent to participate in Study S124. • Patients must have pretreatment tumor tissue available for immediate collection (i.e., tumor tissue obtained for histologic diagnosis of disease before the patient receives any induction chemotherapy). The pretreatment tumor tissue must be formalinfixed and embedded in paraffin (FFPE); blocks are preferred but slides are permitted. • Patients must provide informed consent for tissue collection, analysis, and storage for use in TR activities. [2] For collection of second biopsy specimens: • Patients must have achieved a response of CR, PR, or SD after completion of 4 cycles of induction chemotherapy and be eligible for randomization to maintenance treatment on Study S124. • Patients must provide informed consent for a second biopsy and for tissue collection, analysis, and storage for use in TR activities. The second biopsy will be performed after completing 4 cycles of induction chemotherapy with pemetrexed + cisplatin (and before initiation of maintenenace therapy). The pretreatment tumor tissue must be FFPE; blocks are preferred but slides are permitted. |
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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 patient’s 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 [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 < or = 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 significant (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 < or =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) |
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. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient-reported outcomes and Resource utilization |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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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The trial will end approximately 15 months after the last patient is randomised in the maintenance phase (it is anticipated that by then 260 deaths would have occured) that will be included for the final analysis. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |