E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastaic non-small cell lung cancer, second line therapy |
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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 |
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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 |
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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 the study is to evaluate the anti-tumor activity of LY2181308 in combination with docetaxel therapy (experimental arm) compared to docetaxel alone (standard of care arm) in second line non-small cell lung cancer (NSCLC) patients. |
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E.2.2 | Secondary objectives of the trial |
To characterize and compare the quantitative and qualitative toxicities of LY2181308 combined with docetaxel and docetaxel in this patient population.To compare efficacy variables of both therapies including: Time to Event variables (PFS, Overall survival, Time to worsening of symptoms, Time to objective tumor response, Time to documented disease progression,Objective tumor response, Duration of Response. To evaluate the pharmacokinetics of LY2181308 and docetaxel alone and when combined together. To explore biomarkers relevant to tumor progression and/or survivin expression. To compare changes in the individual item scores, the average symptom burden index (ASBI), and total score of the Lung Cancer Symptom Scale (LCSS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1Histological diagnosis of NSCLC with locally advanced or metastatic disease (Stage IIIB or IV at entry)that is not amenable to curative therapy and who have progressed after 1�line of chemotherapy for advanced disease.Pt who received maintenance treatment will be counted as having received 1�line treatment.Pt who received only single-agent EGFR inhibitors as their 1� treatment must have been treated with a chemotherapy regimen prior to be eligible for this study.2Have given written informed consent.3Presence of measurable disease as defined by the RECIST.4The 1�approximately 15 pt on study (pt enrolled prior to the 1�interim analysis) will have a performance status of 0 to 1 on the ECOG Scale.Remaining pt who are enrolled after the 1�interim analysis will have a performance status of 0 to 2 on the ECOG Scale provided that the 1�interim analysis data do not suggest that PS2 pt may not benefit from the regimen.5Must make available any existing tumor tissue from the primary diagnostic biopsy (mandatory).Biopsy material must be sufficient to allow gene expression assessments.If insufficient amount of tissue is found to be available after pt has been randomized,the pt may remain on study without a protocol violations and this pt must be replaced.6The pt must have tumor lesion amenable for a 2�biopsy.This non-mandatory biopsy will be taken before the 1�dose of study drug and may also be obtained from an extra-pulmonary lesion.Cells isolated from pleural effusions will not be used for this study.If biopsy is performed it must provide sufficient material for gene expression assessments.The failure to obtain this biopsy for any reason will not constitute a protocol violation or prevent the pt participation in this study.7Pt with prior radiation therapy are eligible if they meet the following criteria:Previous radiation therapy is allowed to<25% of the bone marrow but whole pelvis radiation is excluded.Prior radiotherapy must be completed at least 2 weeks before pt is randomized.Pt must have recovered from the acute toxic effects of the treatment before randomized.Prior thoracic radiation must be completed 30 days before study enrollment.Irradiated pulmonary lesions cannot be used as target lesions(must be excluded)unless there is previous documented progression of these lesions.Palliative extrathoracic radiotherapy can continue,but these lesions have to be excluded as target lesions.8Pt compliance and geographic proximity that allow for adequate follow-up:Adequate venous access,Absence of any psychological,familial,sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;those conditions should be discussed with the pt before registration in the trial.9Adequate bone marrow reserve and organ function including:Hematologic:neutrophil count>1.5x109/L,platelets>100x109/L,and hemoglobin>9g/dL.Requirements may be met following transfusions.Hepatic: total bilirubin≤1.25xthe ULN,alanine transaminase (ALT) and aspartate transaminase (AST)≤1.5x ULN,alkaline phosphatase≤5xULN.NOTE:ALT and/or AST elevations>1.5xULN are acceptable with asymptomatic or clinically nonrelevant elevation of these isolated transaminases and with total bilirubin≤1.25xULN.Adequate renal function as assessed by serum creatinine≤1.15xULN.In rare cases, pt may enter treatment with a serum creatinine>1.15xULN,<2.0xULN as elevations of serum creatinine may be secondary to dehydration.This requires prior approval by the Lilly physician and must be consistent with the pt history.10]For women:Must be surgically (or by radiation) sterile, postmenopausal,or compliant with 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 within7days prior the randomization and must not be breast-feading.11At least 18 years old |
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E.4 | Principal exclusion criteria |
12Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. However, patients may be permitted to enter treatment before the 30 day waiting period in special circumstances.13Have previously completed or withdrawn from this study or any other study investigating LY2181308.14Pregnant or breastfeeding (females).15Serious concomitant systemic disorders that would compromise the safety of the patient or compromise the patient s ability to complete the study. These conditions include, but are not limited to, unstable angina, pulmonary embolism, uncontrolled hypertension, history of interstitial pneumonitis or pulmonary fibrosis and unmanageable bleeding risks (at the discretion of the investigator). 16Second primary malignancy that could affect compliance with the protocol or interpretation of the study results. For instance, patients with adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, low-grade (Gleason score ≤6) localized prostate cancer and patients with prior history of malignancy who have been diseasefree for more than 3 years are eligible. [17]Known allergy or hypersensitivity to docetaxel, taxanes, LY2181308, oligonucleotides, or any component of the formulations. 18Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out occult brain metastasis. 19Pre-existing neuropathy equivalent to a CTCAE ≥Grade 2. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in tumor size (CTS) from baseline to the end of Cycle 2. |
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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 | 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 |
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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) | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |