LBH Phase II in Small Cell Lung Cancer (SCLC)

Small Cell Lung Carcinoma Clinical Trial

Official title:

A Phase II Study of the Histone Deacetylase Inhibitor Panobinostat (LBH589) in Patients With Advanced Small Cell Lung Cancer (SCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01222936
• Other study ID #: S075LBH501
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2010
• Last updated: October 14, 2010
• Start date: May 2008
• Est. completion date: August 2010

Study information

• Verified date: October 2010
• Source: Southern Europe New Drug Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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. Combination chemotherapy based on cisplatin or carboplatin and etoposide represents the most widely used regimen. Despite of the high response rate, approximately 80% of patients with limited disease and nearly all patients with extended disease develop disease relapse or progression. Topotecan is, at present, the only approved second line treatment in Europe.

The search of a new therapeutic agent that could alter the natural history of SCLC would be an important goal to be reached. LBH589 (Panobinostat) is a histone deacetylase (HDAC) inhibitor available for intravenous and oral administration. LBH589 could be classified as PAN-DAC inhibitor targeting both histone and non histone proteins and as such it could be suitable for combination with cytotoxics. Three phase I dose escalation studies with both the intravenous and the oral formulation of LBH589, examining various dose schedules of administration have been conducted in advanced solid tumours and haematological malignancies.

Single agent activity was observed in phase I in patients with haematological cancer. In solid tumours one response (Hormone-refractory Prostatic Cancer) and some prolonged stabilizations have been observed with intravenous formulation. Phase II studies are now in progress.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histological/cytological diagnosis of SCLC, mixed small and non small cell tumours are excluded

2. = 2 prior chemotherapy lines

3. Progression after, and not during, last previous chemotherapy treatment

4. Age = 18 and = 75 years

5. Life expectancy of at least 3 months

6. ECOG Performance Status 0-1

7. 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.

8. Adequate haematological function:

• haemoglobin = 9 g/dl

• platelet count = 100,000/mm3

• neutrophils count = 1,500/mm3

9. 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

10. Fertile patients must use effective contraception during and for = 6 weeks after completion of study therapy

11. Ability to signed informed consent

Exclusion Criteria:

1. Progression while on previous chemotherapy

2. Other chemotherapy treatment < 4 weeks prior to enrolment

3. Presence of active infection

4. A known history of HIV positivity

5. Participation to any investigational drug study < 4 weeks preceding study enrolment

6. Radiotherapy involving > 30% of the active bone marrow

7. Thoracic and brain radiotherapy < 4 weeks prior to enrolment. Palliative radiotherapy is allowed during study treatment

8. Presence of any serious neurological or psychiatric disorder

9. 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

10. Known hypersensitivity/allergic reaction to the study product

11. 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.

12. 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.

13. Symptomatic or progressive brain metastases

14. 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

15. Pregnant or lactating women

16. 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.

17. Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF) = 2 weeks prior to starting study drug.

18. Unable or unwilling to comply with all study procedures

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• LBH581
25 mg/5 ml solution packaged in 6 ml type I glass vials and given as a 30 minutes infusion at the dose of 20 mg/m2 i.v., on day 1 and 8, every 21 days.

Locations

Country	Name	City	State
Germany	Klinik für Onkologie und Haematologie	Frankfurt am Main
Germany	Klinikum Kassel Innere Medizin	Kassel
Italy	Azienda Ospedaliera "S. G. Moscati"	Avellino	AV
Italy	Istituto Nazionale Ricerca sul Cancro	Genova	GE
Italy	U.O. di Oncologia Medica	Palermo	PA
Italy	Ospedale Maggiore di Parma	Parma	PR
Italy	Azienda Ospedaliera San Camillo Forlanini	Rome	RM
Italy	Az. San. Ospedaliera Molinette S. Giovanni Battista di Torino	Torino	TO

Sponsors (2)

Lead Sponsor	Collaborator
Southern Europe New Drug Organization	Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	Objective response rate measured according to the RECIST (Response Evaluation Criteria In Solid Tumours).	12-18 weeks (foreseen participation of the patient in the study)	No
Secondary	Duration of antitumor activity	Time-to-progression, duration of response and disease stabilization	12-18 weeks (foreseen participation of the patient in the study)	No
Secondary	Drug safety profile	Evaluation of adverse events, physical examination, vital signs, concomitant medications, laboratory (hematology and chemistry) and instrumental data (i.e. ECG) considered for safety analyses	28 days following the last dose	Yes