E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extensive Disease Small Cell Lung Cancer that is refractory or progressive |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
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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 the objective tumour response rate (RECIST).
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E.2.2 | Secondary objectives of the trial |
• Duration of overall response • Time to tumor progression (TTP) • Progression free survival (PFS) • Overall survival • Toxicity profile • Incidence of cardiomyopathy • Incidence of CNS progression • Pharmacokinetic parameters
There are also exploratory objectives: • ORR based on prior response to first-line therapy • Disease control rate (ORR by RECIST plus SD x 12 weeks) • Duration of disease control |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all the following criteria for inclusion into the study at the time of screening. 1. Histological or cytological diagnosis of SCLC 2. Refractory to first-line platinum-based chemotherapy (i.e., has received one prior platinum-based chemotherapy regimen) defined as one of the following: a. Best response to first-line chemotherapy is radiographically documented progression (refractory disease) b. Best response to first-line chemotherapy is radiographically documented response or stable disease, with subsequent documented progression during continuing chemotherapy (resistant relapse) c. Documented progression within 90 days of completion of first-line chemotherapy (end of last cycle), regardless of best response to treatment (resistant relapse) 3. At least 18 years of age 4. ECOG Performance Status of 0, 1, or 2 5. Measurable disease defined by RECIST criteria. a. Measurable disease: The presence of at least one measurable lesion. If only one lesion is present, the neoplastic nature of the disease site should be confirmed by histology and/or cytology b. Measurable lesion: Lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral CT scans. CT (including spiral CT) scans and MRI are the preferred methods of measurement; however, chest x-rays are acceptable if the lesions are clearly defined and surrounded by aerated lung. Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion is required. 6. Adequate organ function including the following: • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) greater or equal to 1500 cells/μL, platelet count greater or equal to 100,000 cells/μL and hemoglobin greater or equal to 9 g/dL • Hepatic: bilirubin less than or equal to 1.5 X ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3.0 X ULN. • Renal: serum creatinine less than 2.0 mg/dL or calculated creatinine clearance more than 60 mL/min • Cardiac: Left ventricular ejection fraction (LVEF) greater or equal to 50% by MUGA or echocardiography (intra-patient reassessment of LVEF should be performed via the same method throughout the study). 7. Negative serum pregnancy test at the time of enrollment for women of child-bearing potential. For men and women of child-producing potential, use of effective contraceptive methods during the study. 8. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if any of the following apply: 1. Pregnant or nursing women 2. Radiotherapy within the previous 30 days. Recovery from the acute toxic effects of radiation required prior to study enrollment. Measurable lesions that have been previously irradiated must be enlarging to be considered target lesions. Prior radiation therapy allowed to less than 25% of the bone marrow. 3. Prior anthracycline treatment 4. Participation in any investigational drug study within 28 days prior to study entry 5. Patients with second primary malignancy (except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 2 years previously with surgery and or radiotherapy and no evidence of recurrence since that time). 6. Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study. 7. Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable after radiotherapy for 2 weeks or more and off corticosteroids for 1 week or more. 8. History of interstitial lung disease or pulmonary fibrosis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective tumor response rate (RECIST).
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
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) | 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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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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The last visit of the last patient 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |