Panobinostat, Etoposide, and Cisplatin as First-Line Therapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Cancer Trials Ireland

Status and phase

Withdrawn

Phase 1

Conditions

Lung Cancer

Treatments

Other: pharmacological study

Drug: etoposide phosphate

Drug: panobinostat

Other: laboratory biomarker analysis

Drug: cisplatin

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT01160731

ICORG-07-09

EU-21047

EUDRACT-2008-003634-21

07-09 ICORG

Details and patient eligibility

About

RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with etoposide and cisplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with etoposide and cisplatin as first-line therapy in treating patients with extensive-stage small cell lung cancer.

Full description

OBJECTIVES:

Primary

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.

Secondary

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 months.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed small cell lung cancer
- Extensive-stage disease
Measurable disease according to RECIST criteria
No symptomatic brain metastasis or meningeal tumors

PATIENT CHARACTERISTICS:

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 months
- 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