E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IV adenocarcinoma of the lung |
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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 | 10025038 |
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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 |
To compare the effect of farletuzumab or placebo in combination with carboplatin and paclitaxel or docetaxel followed by farletuzumab or placebo and pemetrexed on progression-free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, in chemotherapy-na�ve subjects with folate receptor-alpha (FRA)-expressing Stage IV adenocarcinoma of the lung who do not have the EGFR activating mutations, exon 19 del or exon 21 L858R. |
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E.2.2 | Secondary objectives of the trial |
• To assess the effect of farletuzumab on overall response rate (ORR) • To assess the effect of farletuzumab on duration of response (DR) • To assess the effect of farletuzumab on overall survival (OS) • To assess the safety and tolerability of farletuzumab in combination with carboplatin, paclitaxel or docetaxel and pemetrexed |
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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 |
FARMACOGENETICA: Versione:1 Data:2010/09/02 Titolo:A Randomized, Double-Blind, Placebo-Controlled, Study of the Safety and Efficacy of Farletuzumab in combination with Carboplatin and Paclitaxel or Docetaxel Followed by Pemetrexed in Chemotherapy-naїve Subjects with Stage IV Adenocarcinoma of the Lung with Wild Type EGFR Obiettivi:la ricerca del mRNA servira` a sviluppare una reazione a catena della polimerasi di trascrizione inversa (RT-PCR) per analizzare la presenza del recettore alfa per l`acido Folico.
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E.3 | Principal inclusion criteria |
[1] Female or male and ≥18 years of age [2] Histologically or cytologically confirmed adenocarcinoma of the lung classified as stage IV [3] Wild-type EGFR [4] Adenocarcinoma of the lung must have confirmation of folate receptor-alpha (FRA) expression in ≥5% of tumor cells by immunohistochemistry [5] Measurable disease with at least one unidimensionally measurable lesion according to RECIST criteria version 1.1 by CT or MRI scans (CT or MRI scans must have been performed within 30 days prior to the first dose of farletuzumab or placebo) [6] Must have received no prior chemotherapy, radiation therapy or surgery with curative intent for adenocarcinoma of the lung [7] ECOG performance status (0 or 1) [8] Life expectancy of ≥3 months as estimated by the investigator [9] Adequate bone marrow reserve and organ function including calculated creatinine clearance ≥60 mL/min based on the standard Cockcroft-Gault equation [10] Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to the first dose of farletuzumab or placebo [11] Laboratory and clinical results within 14 days prior to Day 1 must be as follows: Absolute neutrophil count ≥ 1.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L Hemoglobin ≥9 g/dL; Serum bilirubin ≤ 1.5 x ULN; AST/ALT/ALK-P ≤ 2.0 x ULN; Serum creatinine ≤2.0 mg/ dL [12] Subjects of childbearing potential must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period (Contraceptive measures must start either prior to or at screening and continue throughout the entire study period and for 2 months after the last dose of study drug is administered; Pregnant and/or lactating females are excluded) [13] Subject must provide written informed consent and must be able to comply with the protocol procedures |
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E.4 | Principal exclusion criteria |
[1] Subjects who have had previous chemotherapy for adenocarcinoma of the lung [2] Prior surgery with curative intent for adenocarcinoma of the lung XML File Identifier : 5lWStsxaE99yG+Xao+NN2C/Lvms= [3] Prior radiotherapy for adenocarcinoma of the lung. (Prior treatment with local radiotherapy for symptom control [i.e., palliative radiation with non-curative intent] is permitted) [4] EGFR mutation (exon 19 deletion and exon 21 activating mutation L858R) by IHC as assessed by the central laboratory or by PCR assessed by the investigative site [5] Clinically significant cardiovascular disease, congestive heart failure (New York Heart Association Class 3 or 4), clinically significant ventricular arrhythmia requiring medication, or unstable angina within 6 months of study enrolment [6] ECG demonstrating clinically significant arrhythmias (Note: subjects with chronic atrial arrhythmia, i.e. atrial fibrillation or paroxysmal supraventricular tachycardia [SVT] are eligible) [7] Peripheral neuropathy ≥ NCI CTCAE v 3.0 Grade 2 [8] Known untreated brain metastases (Subjects with previously treated, stable brain metastases are allowed. Per investigator’s discretion subject must have fully recovered from radiotherapy or surgery (minimum of 14 days) prior to study entry; steroid or other anti-convulsant treatment must be completed 14 days prior to study entry) [9] Unable or unwilling to take folic acid, vitamin B12, or corticosteroids [10] Concurrent immunotherapy (i.e., immunosuppressants or chronic use of systemic steroids with the exception of low-dose corticosteroids) [11] Known allergic reaction to a prior monoclonal antibody therapy or have any documented HAHA [12] Previous treatment with farletuzumab [13] Active serious systemic disease, including active bacterial or fungal infection [14] Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, psychiatric illness, or social situations that would limit compliance with study requirements [15] Known active human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C infection (Asymptomatic positive serology is not exclusionary) [16] Evidence of other active invasive malignancy requiring treatment in the past 5 years [17] Prior treatment with any investigational agent within 4 weeks of study entry [18] Breast-feeding, pregnant, or likely to become pregnant during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is PFS which is defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (RECIST criteria version 1.1), or date of death, whatever the cause. If progression or death is not observed for a subject, the PFS time will be censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further anti-tumor treatment or the cut-off date, whichever is earliest. Detailed censoring rules will be outlined in the Statistical Analysis Plan. |
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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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | Yes |
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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. Il trattamento durante la terapia di induzione o mantenimento continuera` fino alla progressione della malattia come definito nella versione 1.1 dei criteri RECIST. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |