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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1: To evaluate safety and tolerability of CDP791 given at 10 and 20 mg/kg in combination with carboplatin/paclitaxel in subjects with locally advanced and metastatic (Stage IIIb with malignant pleural effusion or Stage IV) non-squamous non-small-cell lung cancer (NSCLC).Part 2: To compare the tumor response rate of CDP791 given at 10 and 20 mg/kg in combination with carboplatin/paclitaxel with that of carboplatin/paclitaxel alone, in subjects with locally advanced and metastatic (Stage IIIb with malignant pleural effusion or stage IV) non-squamous non-small-cell lung cancer (NSCLC). |
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E.2.2 | Secondary objectives of the trial |
For CDP791 (10 mg/kg or 20 mg/kg) plus carboplatin/paclitaxel versus carboplatin/paclitaxel alone: To compare duration of progression free survival, the overall survival of subjects, time to treatment failure, time to response and response duration, the safety and tolerability in this subject population.
CDP791 (10 mg/kg or 20 mg/kg) given with carboplatin/paclitaxel: To assess pharmacokinetic parameters and immunogenicity
To assess pharmacokinetic parameters of carboplatin and paclitaxel with and without CDP791 (study part 1 only). To measure the effect of carboplatin/paclitaxel and CDP791 on levels of soluble VEGFR-2.
To assess Health-Related Quality of Life (HRQOL) of subjects as measured by the EORTC QLQ-C30 supplemented with the EORTC QLQ-LC13.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male and female subjects with histologically or cytologically confirmed Stage IIIb (with malignant pleural effusion), Stage IV, or recurrent non-squamous, non-small-cell lung carcinoma. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the subject is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy. 2.The subject must be aged 18 years or above. 3.The subject must have ECOG performance status of 0 or 1 and a life expectancy of at least three months. 4.Subjects will have measurable disease defined as at least one lesion that is measurable in one dimension (RECIST evaluation (Therasse P, et al; 2000)). 5.The subject must be able to understand the information provided to them and to give written informed consent. 6.Female subjects must be either postmenopausal (last menstrual period more than two years prior to study), surgically sterilized, or using a method of contraception judged reliable by the Investigator. 7.Male subjects must be using a method of contraception judged reliable by the Investigator. 8.Subjects must have adequate renal function as determined by the following tests within one week prior to randomization:Serum creatinine less than or equal to 1.5 times the upper limit of normal (ULN), AND urine dipstick for proteinuria of less than 1+ (i.e. either 0 or trace).If urine dipstick is > 1+ then a 24 hour urine for protein must demonstrate < 500 mg of protein in 24 hours to allow participation in the study. |
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E.4 | Principal exclusion criteria |
1.Subjects with squamous cell lung carcinoma. 2.Subjects with lung lesions located centrally in the chest that involve major blood vessels. 3.Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for five years or more. 4.Presence of additional major chronic disease such as hepatic or renal dysfunction, cardiac dysfunction, peripheral vascular disease, evidence of a myocardial infarction within six months of Screening visit, tuberculosis or epilepsy. 5.Subjects known to be infected with hepatitis B or C virus or HIV 1 or 2. 6.Any evidence of serious active infection (ie requiring an iv antibiotic or antiviral agent). 7.Subjects should not have abnormal organ function indicated by: · Bilirubin greater than the ULN· AST or ALT greater than 2.5 times ULN (no liver metastases)· AST or ALT greater than 5 times ULN (liver metastases present)· Creatinine greater than 1.5 times ULN· Proteinuria greater than Grade 1 NCI CTC· Hemoglobin less than 9g/dL (subjects may be transfused to meet this requirement) White cell count less than 3 x 10(9)/L · Absolute neutrophil count less than 1500/mm³ Platelet count less than 100 x 10(9)/L· Abnormal activated partial thromboplastin time (APTT)· Abnormal prothrombin time (PT)
8.Subjects who have or who are suspected to have brain metastases. A head CT or MR is required within four weeks of study entry. 9.Major surgery within four weeks or open biopsy within one week of planned study drug administration. 10.Non healing wound or ulcer. 11.Previous chemotherapy or immunotherapy (registered, off label or experimental). 12.Radiotherapy within two weeks of first dose of study drug. 13.History of clinically significant adverse reaction to biological products or polyethylene glycol. 14.Known alcohol or drug dependency. 15.Subjects must not weigh more than 150 kg. 16.Subjects must not be pregnant or breast feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The tumor response rate (RR) will be defined as the total number of subjects whose best response is a complete response (CR) or a partial response (PR), divided by the number of randomized subjects. Primary analysis of RR will be a comparison of this endpoint between the pooled carboplatin/paclitaxel + 10 mg/kg or 20 mg/kg treatment arms and the carboplatin/paclitaxel alone treatment arm, using a two-sided chi-square test. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | 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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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At the time all subjects are either discontinued or on study for at least 24 weeks, the study will be considered as ready for database lock and analysis. As an administrative definition, the end of study will be considered as the final database lock. However, follow-up data will continue to be collected regarding tumor assessments until documented progressive disease, for further analysis updates. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |