E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic non-squamous second-line Non-small cell lung cancer |
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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 | 10029521 |
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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 | 10029522 |
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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 this study is to estimate the overall response rate (ORR) for patients receiving pemetrexed in combination with LY2603618 for advanced or metastatic non-small cell lung cancer (NSCLC) after 1 prior therapy for their disease |
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E.2.2 | Secondary objectives of the trial |
To characterize the safety and toxicity profile of LY2603618 when administered in combination with pemetrexed in the above patient population. To estimate time-to-event variables, such as progression free survival (PFS) and duration of response. To evaluate the clinical benefit rate (clinical benefit rate = best response of stable disease [SD] + partial response [PR] + complete response [CR] per Response Evaluation Criteria in Solid Tumors [RECIST]). To further evaluate the pharmacokinetics of LY2603618 in combination with pemetrexed. To determine if MAGEA2 and CDKN2A gene expression correlates with tumor protein 53 (TP53) mutation status and/or p53 expression in tumor biopsies. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histological or cytological diagnosis of advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) which has progressed after first line treatment with a platinum doublet chemotherapy regimen not containing pemetrexed. Previous treatment with biological agents is permitted. [2] Patients must agree to (and be clinically able to undergo) a biopsy of the primary tumor or an accessible metastasis during the baseline Visit (Visit 0). [3] Have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 definitions. At least 1 measurable lesion must be outside the field of any allowed prior radiotherapy; see Exclusion Criterion [11]. [4] Have a performance status of &#8804;2 on the Eastern Cooperative Oncology Group (ECOG) scale. [5] Males or females at least 18 years of age. Have adequate organ function including: Hematologic: Absolute neutrophil count (ANC) &#8805;1.5 x 109/L, platelets &#8805;100 x 109/L, and hemoglobin &#8805;9 g/dL. Transfusions are allowed to meet this requirement.Hepatic: Bilirubin &#8804;1.5 times upper limits of normal (ULN), aspartate transaminase (AST) <2.5 times ULN, alanine transaminase (ALT) &#8804;2.5 times ULN. If the liver has tumor involvement, aspartate transaminase (AST) <5 times ULN and ALT equaling &#8804;5 times ULN are acceptable. Patients may have endoscopic or radiologic stenting to treat biliary obstructions. If so, then bilirubin must return to <1.5 times ULN, alkaline phosphatase (AP) and aspartate transaminase (AST) to <5 times ULN, and ALT to &#8804;5 times ULN prior to enrollment. Renal: Calculated creatinine clearance (Cockroft-Gault formula; see Protocol Attachment JMMD.4), greater than or equal to 45 mL/min.Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow (Christy and Eckerman 1987) and patients must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry. At least 1 measurable lesion must be outside the previous radiotherapy field. |
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E.4 | Principal exclusion criteria |
Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving the use of an investigational drug or device (other than the study drug 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. [14] Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris or uncontrolled diabetes mellitus).Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography (CT) scan or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response is an appropriate primary endpoint in a single arm trial. Progression-free survival, duration of response, and clinical benefit are accetable secondary endpoints and are clinically relevant in patients with life-threatening diseases |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | |
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 |