LBH Phase II in Small Cell Lung Cancer (SCLC)

NCT01222936 | Completed Phase 2

• 1 other identifier: S075LBH501
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 8

Brief 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.

Conditions

Small Cell Lung Carcinoma

Keywords

LBH581; Panobinostat; Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (2)

• Duration of antitumor activity

  12-18 weeks (foreseen participation of the patient in the study)

• Drug safety profile

  28 days following the last dose

Interventions

LBH581 DRUG

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.

Also known as: Panobinostat

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Southern Europe New Drug Organization: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (8)

Klinik für Onkologie und Haematologie

Frankfurt am Main, 60488, Germany

Location

Klinikum Kassel Innere Medizin

Kassel, 34125, Germany

Location

Azienda Ospedaliera "S. G. Moscati"

Avellino, AV, 83100, Italy

Location

Istituto Nazionale Ricerca sul Cancro

Genova, GE, 16132, Italy

Location

U.O. di Oncologia Medica

Palermo, PA, 90141, Italy

Location

Ospedale Maggiore di Parma

Parma, PR, 43100, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, RM, 00151, Italy

Location

Az. San. Ospedaliera Molinette S. Giovanni Battista di Torino

Torino, TO, 10126, Italy

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Filippo De Marinis, MD

  Azienda Ospedaliera San Camillo Forlanini

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 11, 2010
• First Posted: October 18, 2010
• Study Start: May 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: August 1, 2010
• Last Updated: October 18, 2010

Record last verified: 2010-10

Locations

IT (6); DE (2)