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

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ClinicalTrials.gov Identifier: NCT01160731
Recruitment Status : Withdrawn
First Posted : July 12, 2010
Last Update Posted : December 31, 2014
Sponsor:
Information provided by (Responsible Party):
Cancer Trials Ireland

Tracking Information
First Submitted Date  ICMJE July 9, 2010
First Posted Date  ICMJE July 12, 2010
Last Update Posted Date December 31, 2014
Study Start Date  ICMJE November 2009
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2010)
  • Maximum-tolerated dose (MTD) and recommended dose (RD)
  • Response rates and toxicity at MTD and RD
  • Objective response rate according to RECIST criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01160731 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2010)
  • Time to progression according to RECIST criteria
  • Duration of response or disease stabilization according to RECIST criteria
  • Overall survival according to RECIST criteria
  • Effect of the combination regimen on drug pharmacokinetics
  • Adverse events
  • Quality of life evaluated by EQ-5D (Euro QoL)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Panobinostat, Etoposide, and Cisplatin as First-Line Therapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer
Official Title  ICMJE 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
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Drug: cisplatin
  • Drug: etoposide phosphate
  • Drug: panobinostat
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Study Arms  ICMJE Experimental: Cisplatin, Etoposide & Panobinostat
Interventions:
  • Drug: cisplatin
  • Drug: etoposide phosphate
  • Drug: panobinostat
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 26, 2012)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2010)
24
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Ireland,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01160731
Other Study ID Numbers  ICMJE 07-09 ICORG
ICORG-07-09
EUDRACT-2008-003634-21
EU-21047
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cancer Trials Ireland
Study Sponsor  ICMJE Cancer Trials Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul Donnellan Galway University Hospital
PRS Account Cancer Trials Ireland
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP