E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 100000004864 |
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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 co-primary objectives of this study are to compare Abemaciclib plus BSC versus erlotinib plus BSC with respect to overall survival (OS)
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare Abemaciclib plus BSC to erlotinib plus BSC with respect to:
• overall response rate (complete response [CR] + partial response [PR])
• progression-free survival (PFS)
• changes in patient-reported pain and disease-related symptoms collected via the MD Anderson Symptom Inventory (MDASI-LC) and changes in health status via European Quality of Life – 5 Dimensions – 5 Level (EQ-5D 5L).
• safety and tolerability
• resource utilization (for example, analgesic type, hospitalization, transfusion)
Additional Secondary objective is to examine the pharmacokinetic (PK)/pharmacodynamic properties of Abemaciclib
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The participants must have confirmed diagnosis of stage IV non-small cell lung cancer (NSCLC) according to the American Joint Committee on Cancer Staging Handbook.
• Determined to have detectable mutations in codons 12 or 13 of the KRAS oncogene by an investigational assay at the Study JPBK central laboratory. A KRAS positive mutation result in codons 12 or 13 of the KRAS Oncogene from tumor tissue per local laboratory will be permitted on no more than 10% of the randomized patients;
• The participant must have progressed after platinum-based chemotherapy (with or without maintenance therapy) AND have received one other additional therapy which may include an immune checkpoint inhibitor or other anti-cancer therapy for advanced and/or metastatic disease OR is judged by the physician as ineligible for further standard second-line chemotherapy. Prior adjuvant or neoadjuvant therapy for an earlier stage of NSCLC counts as an appropriate line of therapy in case the patient progressed within 6 months of completing the platinum-based adjuvant or neoadjuvant therapy.
• Have measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug.
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E.4 | Principal exclusion criteria |
• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
• Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Have the presence of unstable central nervous system (CNS) metastasis. History of CNS metastasis or stable CNS metastases is allowed (no longer requiring active therapy such as steroid medications). Participants with a history of CNS metastases must have a brain scan (for example, magnetic resonance imaging) within 28 days of randomization to document stability, even if there have been no changes in symptoms.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
OS: Baseline and every cycle up to Date of Death from Any Cause (Estimated up to 34 Months)
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E.5.2 | Secondary end point(s) |
- Proportion of Participants Achieving Either Complete or Partial Response (Overall Response Rate)
- PFS: Baseline and every other cycle up to objective progression or Death from Any Cause
- Change from Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Score and in European Quality of Life - 5 Dimensions - 5 Level (EQ-5D-5L) Score
- Safety and tolerability
- Resource Utilization: Percentage of Participants Who are Hospitalized
- Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2835219 (Abemaciclib)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Overall Response Rate: Baseline and every other cycle up to Objective Progression or Death from Any Cause (Estimated up to 34 Months)
- PFS: Baseline and every other cycle up to Objective Progression or Death form Any Cause (Estimated up to 34 months)
- MDASI-LC Score and EQ-5D-5L Score: Baseline and every cycle up to 30 days after treatment discontinuation
- Safety and tolerability: every visit
- Resource Utilization: every visit up to 30 days after treatment discontinuation
- AUC of LY2835219 (Abemaciclib): Cycles 1, 2 and 3
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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 | 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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Argentina |
Austria |
Brazil |
Canada |
China |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
Turkey |
Ukraine |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |