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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01160731
• Other study ID #: 07-09 ICORG
• Secondary ID: ICORG-07-09EUDRA
• Status: Withdrawn
• Phase: Phase 1
• First received: July 9, 2010
• Last updated: December 30, 2014
• Start date: November 2009

Study information

• Verified date: October 2012
• Source: ICORG- All Ireland Cooperative Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Medicines Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy

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

Study Design

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• cisplatin

• etoposide phosphate

• panobinostat

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ICORG- All Ireland Cooperative Oncology Research Group

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated dose (MTD) and recommended dose (RD)			No
Primary	Response rates and toxicity at MTD and RD			Yes
Primary	Objective response rate according to RECIST criteria			No
Secondary	Time to progression according to RECIST criteria			No
Secondary	Duration of response or disease stabilization according to RECIST criteria			No
Secondary	Overall survival according to RECIST criteria			No
Secondary	Effect of the combination regimen on drug pharmacokinetics			No
Secondary	Adverse events			Yes
Secondary	Quality of life evaluated by EQ-5D (Euro QoL)			Yes