E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SCLC is the most aggressive and lethal form of lung cancer, typically very sensitive to cytotoxic therapy when first diagnosed, but associated with a high incidence of tumour relapse and a very poor life expectancy. Despite the high response rate, approximately 80% of patients with limited disease and nearly all patients with extended disease develop disease relapse or progression. |
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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 | 10041067 |
E.1.2 | Term | Small cell lung cancer |
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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 assess the antitumor activity of LBH589 as single agent given i.v. in patients previously treated with no more than 2 previous chemotherapy lines. |
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E.2.2 | Secondary objectives of the trial |
To assess the duration of antitumor activity. To assess the safety profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Histological/cytological diagnosis of SCLC, mixed small and non small cell tumours are excluded · ≤ 2 prior chemotherapy lines · Progression after, and not during, last previous chemotherapy treatment · Age ≥ 18 and ≤ 75 years · Life expectancy of at least 3 months · ECOG Performance Status 0-1 · At least one measurable lesion according to modified RECIST criteria: defined as ≥ 1 lesion with longest diameter ≥ 20 mm by conventional techniques or ≥ 10 mm with spiral CT scan. In case of solitary measurable leasion histological confirmation is not required. · Adequate haematological function: - haemoglobin ≥ 9 g/dl - platelet count ≥ 100,000/mm3 - neutrophils count ≥ 1,500/mm3 · Adequate liver and renal functions: - Total serum bilirubin ≤ 1.5 x UNL - Serum creatinine ≤ 1.5 x UNL or 24 hours creatinine clearance ≥ 50 mL/min - AST and ALT ≤ 2.5 x UNL or ≤ 5.0 x UNL if the transaminase elevation is due to hepatic involvement - Albumin ≥ 2.5 g/dl - Alkaline phosphatase ≤ 2.5 x UNL · Fertile patients must use effective contraception during and for ≥ 6 weeks after completion of study therapy · Ability to signed informed consent
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E.4 | Principal exclusion criteria |
· Progression while on previous chemotherapy · Other chemotherapy treatment < 4 weeks prior to enrolment · Presence of active infection · A known history of HIV positivity · Participation to any investigational drug study < 4 weeks preceding study enrolment · Radiotherapy involving > 30% of the active bone marrow · Thoracic and brain radiotherapy < 4 weeks prior to enrolment. Palliative radiotherapy is allowed during study treatment · Presence of any serious neurological or psychiatric disorder · Impaired cardiac function, including any one of the following - Complete Left Bundle Branch Block or obligate use of a cardiac pacemaker or congenital long QT syndrome or history or presence of atrial or ventricular tachyarrhythmias or clinically significant resting bradycardia (< 50 beats per minute) or QTcF > 480 msec on screening ECG or Right Bundle Branch block + left anterior hemiblock (bifasicular block) - Other clinically significant heart disease (e.g. congestive heart failure, angina pectoris, myocardial infarction within ≤ 3 months prior to starting study drug, uncontrolled hypertension, history of labile hypertension or arrhythmia, or history of poor compliance with an antihypertensive regimen) - Any other case of current abnormal cardiac functionality or history of cardiac disease causing LVEF < 45% as determined by ECHO · Known hypersensitivity/allergic reaction to the study product · Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study. · Previous or current concomitant malignancy at other site, other than basal or squamous cell carcinoma of the skin and carcinoma in situ of the uterine cervix, within 3 years · Symptomatic or progressive brain metastases · Patients with an active bleeding diathesis or on anticoagulants. Therapeutic doses of sodium warfarin (Coumadin) are not allowed. Low doses of Coumadin (e.g., ≤ 2 mg/day) for line patency are allowed · Pregnant or lactating women · Concomitant use of CYP3A4/5 inhibitors or inducers, or drugs that prolong the QT interval and/or induce torsades de pointes ventricular arrythmia, where the treatment can not be discontinued or switched to a different medication prior to starting study drug (medications listed in the following web site http://medicine.iupui.edu/flockhart/table.htm). · Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF) ≤ 2 weeks prior to starting study drug. · Unable or unwilling to comply with all study procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate measured according to modified RECIST criteria. |
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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 | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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) | 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 | 3 |
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 | 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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The number of cycles will be defined by the investigators on the basis of the patient's global clinical evaluation. Treatment can be continued until tumor progression, unacceptable toxicity or patient's refusal, whichever occurs earlier. |
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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 |