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A Phase I Dose Finding Study of the Pan-DAC Inhibitor Panobinostat (LBH589) in Combination With Etoposide and Cisplatin in the First Line Treatment of Extensive-Stage Small Cell Lung Cancer - An ICORG In-House Study

Phase 1
18 Years
Not Enrolling
Lung Cancer

Thank you

Trial Information

A Phase I Dose Finding Study of the Pan-DAC Inhibitor Panobinostat (LBH589) in Combination With Etoposide and Cisplatin in the First Line Treatment of Extensive-Stage Small Cell Lung Cancer - An ICORG In-House Study



- To determine the maximum-tolerated dose, the recommended dose, and the activity of
panobinostat when given in combination with etoposide and cisplatin to patients with
extensive-stage small cell lung cancer.


- To estimate the time-to-progression, the duration of response, and disease
stabilization in these patients.

- To estimate the overall survival of these patients.

- To determine the pharmacokinetic profile of panobinostat in combination with etoposide
and cisplatin.

- To assess the overall safety profile of panobinostat in these patients.

- To determine the adverse events in these patients treated with this regimen.

- To assess the quality of life of these patients.

OUTLINE: This is a multicenter, dose-escalation study of panobinostat.

Patients receive chemotherapy comprising cisplatin IV on day 1, etoposide IV on days 1-3,
and panobinostat IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up
to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then periodically during study treatment and
follow up, using questionnaire EQ-5D (Euro QoL).

Blood samples may be collected at baseline and periodically during and after study treatment
for pharmacokinetic assessment and biomarker translational studies.

After completion of study treatment, patients are followed up at 4 weeks and then every 3

Inclusion Criteria


- Histologically or cytologically confirmed small cell lung cancer

- Extensive-stage disease

- Measurable disease according to RECIST criteria

- No symptomatic brain metastasis or meningeal tumors


- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- Absolute neutrophil count > 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10.0 g/dL

- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR 24-hour creatinine clearance
≥ to 60 mL/min

- Magnesium, potassium, and phosphorus ≥ the lower limit of normal OR correctable with
supplements prior to study treatment

- AST/ALT ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases are present)

- Serum bilirubin ≤ 1.5 x ULN

- Alkaline phosphatase ≤ 2.5 x ULN OR liver fraction ≤ 2.5 x ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double contraception (at least 1 barrier method)
during and for at least 30 days after completion of study treatment

- No impaired cardiac function, including any one of the following:

- LVEF < 45% as determined by ECHO

- Complete left bundle branch block, obligate use of a cardiac pacemaker,
congenital long QT syndrome, history or presence of atrial or ventricular
tachyarrhythmias, clinically significant resting bradycardia (< 50 beats per
minute), QTcF > 480 msec on screening ECG, or right bundle branch block and left
anterior hemiblock (bifascicular block)

- Uncontrolled angina pectoris or acute myocardial infarction within the past 3

- Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen)

- No history of HIV or AIDS-related illness

- No acute or chronic liver or renal disease

- No other concurrent severe and/or uncontrolled medical conditions that could cause
unacceptable safety risks or compromise compliance with the protocol, including any
of the following:

- Uncontrolled diabetes

- Chronic obstructive or chronic restrictive pulmonary disease

- Active or uncontrolled infection

- No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to panobinostat, cisplatin, or etoposide

- No hearing impairment that would be a contraindication to the use of cisplatin


- No prior chemotherapy

- No investigational drug or experimental medications or treatments within the past 30
days or 5 half-lives, whichever is longer

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (MTD) and recommended dose (RD)

Safety Issue:


Principal Investigator

Paul Donnellan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Galway University Hospital


Ireland: Irish Medicines Board

Study ID:




Start Date:

November 2009

Completion Date:

Related Keywords:

  • Lung Cancer
  • extensive stage small cell lung cancer
  • Lung Neoplasms
  • Small Cell Lung Carcinoma