| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent or Advanced Non-Small Cell Lung Cancer with Non-Squamous Histology. |
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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 | PT |
| E.1.2 | Classification code | 10061873 |
|
| 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 is to compare the Progression free survival (PFS) of CT-322 versus bevacizumab in combination with carboplatin and paclitaxel in chemonaive subjects with recurrent or advanced non-squamous NSCLC. |
|
| E.2.2 | Secondary objectives of the trial |
To compare overall survival (OS) between the two treatment arms To compare the objective tumor response rate (ORR) between the two treatment arms To evaluate the safety in the CT-322 plus carboplatin and paclitaxel arm.
Exploratory objectives: To estimate the duration of response and time to response in each of the two treatment arms To evaluate the pharmacokinetics of CT-322 and paclitaxel when administered in combination. An exploratory assessment of predictive and pharmacodynamic markers of CT-322 or bevacizumab administered in combination with carboplatin and paclitaxel will be performed by analyzing pre- and post-treatment specimens, including whole blood, serum or plasma and possibly tumor biopsies. |
|
| 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 |
FARMACOCINETICA/FARMACODINAMICA: Versione:2.0 Data:2009/08/06 Titolo:Sottostudio PK Obiettivi:A 14 pazienti circa verranno raccolti campioni addizionali di sangue per misurare la concentrazione plasmatica di CT-322 come riportato nella tabella 6.5.1.2 (in aggiunta ai campioni che verranno raccolti secondo I tempi ripostati nella tabella 6.5.1.1). Si veda sezione del protocollo (Paclitaxel Pharmacokinetic Sample Collection and Handling).
Nei centri in cui tale sottostudio sara` condotto, sara` utilizzato un modulo di consenso informato per il paziente.
ALTRI SOTTOSTUDI: Sottostudio FDG-PET.
Si veda la sezione 6.4.2.1 (Metabolic response based on FDG-PET).
|
|
| E.3 | Principal inclusion criteria |
| 1) Signed Written Informed Consent 2) Target Population a) Histologically or cytologically confirmed, stage IIIB (malignant pleural effusion), stage IV or recurrent NSCLC; b) Measurable disease by RECIST guidelines, with at least 1 target lesion outside any previous radiotherapy field (also see Section 6.4.1); c) ECOG performance status < 1 (see Appendix 2); d) Life expectancy of at least 3 months; e) Accessible for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating center(s). f) Willing to give a whole blood sample for the study of proteins and genetic polymorphisms in genes related to the VEGFR signaling pathway. 3) Age and Sex a) Men and women, ages >18 years. Men and women of childbearing potential (WOCBP) participating to this trial must be using an adequate method of contraception to avoid pregnancy throughout the study [and for up to 6 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. |
|
| E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period [and for up to 6 weeks after the last dose of investigational product] b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration d) Sexually active fertile men not using effective birth control if their partners are WOCBP. 2) Target Disease Exceptions a) Evidence of predominantly squamous-cell histology (mixed cell type tumors only) b) Known central nervous system (CNS) metastasis 3) Medical History and Concurrent Diseases a) At the time of randomization less than 28 days elapsed following major surgery or radiotherapy (less than 7 days elapsed following minor surgery or focal/palliative RT) b) Excessive risk of bleeding such as history of clinically significant bleeding diathesis or coagulopathy including platelet function disorder (eg, known hemophilia or von Willebrand disease) or acquired bleeding disorder within 12 months (eg, acquired anti-factor VIII antibodies) c) Gross hemoptysis (≥ 1/2 teaspoon (or ≥2.5 ml) of red blood d) Subjects receiving therapeutic anticoagulation, however low doses of aspirin (≤ 325 mg) are permitted e) Thrombotic or embolic cerebrovascular accident including transient ischemic attacks within the past 12 months f) Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg or diastolic > 90 mmHg, measured repeatedly at ≥2 visits despite adequate treatment with ≥ 2 antihypertensive drugs) g) Clinically significant cardiovascular disease, including (but not limited to) the following: i) Myocardial infarction within the past 6 months ii) Unstable angina iii) New York Heart Association class II-IV congestive heart failure (see Appendix 3) iv) Serious cardiac arrhythmia (eg ventricular arrhythmia, high-grade atrioventricular block), not controlled by medication or requiring medication which might interfere with regularity of study treatment v) Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) as measured by 2-dimensional echocardiogram (ECHO) or cardiac MUGA scan (MUGA) h) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months i) Serious non-healing wound, active peptic ulcer, non-healing bone fracture, or bleeding skin metastases j) Glomerulonephritis or other protein-wasting glomerulopathy k) Active clinically significant infection(> Grade 2) requiring the use of antimicrobial agents, or that would otherwise, in the opinion of the investigator, interfere with the ability the subject to participate l) Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma/dysplasia in-situ of the cervix or bladder. Subjects with a history of previous malignancies but without evidence of disease for 4 years and for which no additional therapy is required or anticipated will be allowed to enter the trial. m) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent n) Any serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive study therapy. o) Known HIV positive.
For the others Exclusion critria, see the trial Protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary efficacy assessment is Progression Free Survival and is based on tumor assessments (CT scans/MRI) that will be performed every 6 weeks until documented PD, death or initiation of subsequent therapy for NSCLC. Safety will be evaluated weekly for all treated subjects. Additional assessments include: metabolic response based on FDG-PET, pharmacokinetic, pharmacodynamics, pharmacogenomic/pharmacogenetic and immunogenicity assessments. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 |
|
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
|
| 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
|
| Fino a progressione della malattia inizio di una terapia successiva per NSCLC, i pazienti continueranno ad essere seguiti ogni 12 mesi per la sopravvivenza. |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
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