E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Non-small cell lung cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 (control or 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 (progression-free survival, overall survival, time to worsening of symptoms, time to objective tumour response, time to documented disease progression), objective tumour response rate, duration of response
- To evaluate the PK of LY2181308 and docetaxel alone and when combined
- To explore biomarkers relevant to tumour 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 |
• Patients with non-small cell lung cancer with locally or advanced metastatic disease(Stage IIIB or IV at entry) not amenable to curative therapy and who have progressed after 1 line of chemotherapy
• Measureable disease as defined by response evaluation criteria in solid tumors (RECIST)
• ECOG Performance status of 0 to 1
• Must make available any existing tumor tissue from the primary biopsy
• Patients with prior radiation may be eligible if they meet certain criteria
• Adequate bone marrow reserve and organ functioning
• Women must have a negative pregnancy test and must comply with a highly reliable contraceptive method during and for 6 months after the treatment period. Must not be breastfeeding
• Men must comply with a contraceptive regimen during and for 6 months after the treatment period |
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E.4 | Principal exclusion criteria |
• Currently enrolled in or discontinued a clinical trial involving an investigational drug/device within the last 30 days. Patients may be permitted to enter treatment before the 30 day waiting period in special circumstances
• Pregnant or breastfeeding
• Serious concomitant systemic disorders that would compromise the safety of the patient or the patient's ability to complete the study
• Second primary malignancy that could affect compliance with the protocol or interpretation of the study results
• Known allergy or hypersensitivity to docetaxel, taxanes, LY2181308, oligonucleotides, or any component of the formulations
• Patients with documented central nervous system or brain metastasis at the time of study entry
• Pre-existing neuropathy equivalent to a common terminology criteria for adverse events(CTCAE)code greater than or equal to 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in tumor size; from baseline to the end of Cycle 2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Characterization of toxicities as defined by common terminology criteria for adverse events (CTCAE) coding
Progression Free Survival
Population Pharmacokinetics,including concentration of LY2181308 and docetaxel
Overall Survival
Time to worsening of symptoms as defined by Lung Cancer Symptom Score (LCSS) questionnaire
Time of Objective tumor response of Partial Response (PR) or Complete Response (CR)
Time to documented disease progression
Percent of patients having a Partial Response (PR) or a Complete Response (CR)
Duration of Response
Change from baseline through 30 day follow up in Average Symptom Burden Index (ASBI)
Change from baseline through 30 day follow up in Lung Cancer Symptom Scale (LCSS)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every cycle, 30 day follow up and long term follow up (every 6 weeks until progression then every 60 days for survival or until study ends)
Randomization to the first date of progressive disease or death from any cause
Lead in phase, Cycle 1, Cycle 2 then every other Cycle, 30 day follow up visit
Randomization to date of death from any cause
Baseline to the worsening of symptoms (30 day follow up)
Randomization to the date of first response
Randomization to the first date of progressive disease
Randomization to the first date of progressive disease
Time of response to progressive disease
Baseline, 30 day follow up
Baseline, 30 day follow up
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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 |
Patient reported outcomes |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 27 |
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 | No |
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 |
Belgium |
Germany |
Italy |
Poland |
United Kingdom |
United States |
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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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |