E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable, metastatic non-small cell lung cancer (NSCLC) |
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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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 |
To estimate the time-to-progressive disease for patients who have received LY573636 after two prior treatment regimens of systemic therapy for unresectable, metastatic non-small cell lung cancer (NSCLC). |
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E.2.2 | Secondary objectives of the trial |
• To characterize the progression-free survival distribution • To estimate the objective response rate (complete response [CR] and partial response [PR]) and clinical response rate (CR+PR+stable disease) • To evaluate the pharmacokinetics of LY573636 using a limited sampling methodology in this population • To estimate time-to-event variables, such as overall survival time, duration of overall objective response (up to 1 year), and duration of stable disease (up to 1 year) • To evaluate the safety of LY573636 in this patient population. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients who: [1] Have a histologic and/or cytologic diagnosis of metastatic NSCLC that is unresectable. Patients with unresectable, Stage IIIB disease are also eligible. [2] Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). [3] Are at least 18 years of age. [4] Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale. [5] Have received two previous systemic treatment regimens for metastatic NSCLC, one of which must have been platinum-based. [6] Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, or other investigational therapy for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). [7] Have adequate organ function including: • Bone Marrow Reserve: Absolute neutrophil count (ANC) ≥1.5 x 109/L prior to treatment, platelets ≥100 x 109/L, and hemoglobin ≥8 g/dL (transfusions are not allowed to reach 8 g/dL prior to enrollment). • Hepatic: Bilirubin <1.5 times the upper limit of normal (ULN). Alkaline phosphatase and transaminases (ALT and AST) <5 times ULN • Renal: Serum creatinine at or below the ULN. No known active renal disease [8] Have a serum albumin level ≥ 30 g/L or 3.0 g/dL. [9] Males and females with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug. [10] Exhibit patient compliance and geographic proximity that allow for adequate follow-up. [11] Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site. |
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E.4 | Principal exclusion criteria |
Patients who: [12] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [13] Have received ≥ 3 previous systemic treatment regimens for metastatic NSCLC. [14] Patients 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. [15] Patients with serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator). [16] Patients with a second primary malignancy that could affect compliance with the protocol or interpretation of the results. NOTE: Patients with adequately treated carcinoma of the skin (excluding melanoma) and patients with a prior history of malignancy who have been disease-free for more than 2 years are eligible. [17] Patients with serious preexisting medical conditions (at the investigator’s discretion). [18] Patients actively receiving warfarin (Coumadin®) therapy for treatment of venous thrombosis or other prothrombotic conditions. NOTE: Patients receiving low dose (1 mg daily) warfarin will be allowed in this study. For those patients, more frequent monitoring of PT (INR)/aPTT will be required. [19] Persons who have previously completed or withdrawn from this study or any other study investigating LY573636. [20] Women who are pregnant or lactating. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To estimate time-to-progressive disease and 90% confidence limits for this patient population. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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.8.5 | 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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Following a 12 month enrollment period, the study is designed to end 12 months after the last enrolled patient receives his or her first cycle of LY573636. If at the end of the study period a patient continues to benefit from treatment, then he or she may continue on treatment until clinical or objective disease progression (with the agreement of the investigator and the Lilly clinical research physician [CRP]). |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |