LBH Phase II in Small Cell Lung Cancer (SCLC)

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 lesion, 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

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 (biphasic block)
• Acute MI ≤ 3 months prior to starting study drug
• Other clinically significant heart disease (e.g. congestive heart failure, previous history angina pectoris, 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 drug that prolong the QT interval and/or induce torsades ventricular arrythmia, where the treatment can not be discontinued or switched to a different medication prior to starting study drug.
• 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