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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01160731
First received: July 9, 2010
Last updated: October 26, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: cisplatin
Drug: etoposide phosphate
Drug: panobinostat
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) and recommended dose (RD) [ Designated as safety issue: No ]
  • Response rates and toxicity at MTD and RD [ Designated as safety issue: Yes ]
  • Objective response rate according to RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression according to RECIST criteria [ Designated as safety issue: No ]
  • Duration of response or disease stabilization according to RECIST criteria [ Designated as safety issue: No ]
  • Overall survival according to RECIST criteria [ Designated as safety issue: No ]
  • Effect of the combination regimen on drug pharmacokinetics [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]
  • Quality of life evaluated by EQ-5D (Euro QoL) [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: November 2009
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin, Etoposide & Panobinostat Drug: cisplatin Drug: etoposide phosphate Drug: panobinostat Other: laboratory biomarker analysis Other: pharmacological study

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160731

Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
Investigators
Principal Investigator: Paul Donnellan Galway University Hospital
  More Information

No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT01160731     History of Changes
Other Study ID Numbers: CDR0000680803, ICORG-07-09, EUDRACT-2008-003634-21, EU-21047
Study First Received: July 9, 2010
Last Updated: October 26, 2012
Health Authority: Ireland: Irish Medicines Board

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
extensive stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Panobinostat
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014