Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
Phase I/II Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers
This study is currently recruiting participants.
Verified by H. Lee Moffitt Cancer Center and Research Institute, December 2008
Sponsors and Collaborators: H. Lee Moffitt Cancer Center and Research Institute
Genentech
Novartis
Information provided by: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00738751
  Purpose

The purpose of the study is to:

  • Find out if Erlotinib and LBH589 can be safely given together in patients with advanced non-small cell lung cancer (NSCLC) or Head and Neck (H&N) Cancer.
  • Learn more about the side effects of these two drugs when combined together.
  • Learn how these two drugs work in cancer cells when they are combined.
  • Learn how this combination affects the ways in which they are absorbed by the body and eliminated.
  • Find the highest doses of Erlotinib and LBH589 that can be safely given without causing serious side effects.

Condition Intervention Phase
Lung Cancer
Head and Neck Cancer
Drug: LBH589
Drug: erlotinib
Phase I
Phase II

MedlinePlus related topics: Cancer Head and Neck Cancer Lung Cancer
Drug Information available for: Erlotinib Erlotinib hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase I/II Study of LBH589 in Combination With Erlotinib for Advanced Aerodigestive Tract Cancers (CLBH5889CUS11T)

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Determine safety and tolerability of erlotinib and LBH589B and establish a recommended phase II expansion dosing of LBH589B and erlotinib in patients with advanced aerodigestive tract cancers. [ Time Frame: Dependent upon results ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate safety of erlotinib/LBH589B, pharmacokinetic drug levels of Erlotinib, full profile of single agent vs. combination; biomarkers of acetylation; objective response rate; 6-mo. progression free survival rate; time-to-event variables. [ Time Frame: Dependent upon results ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 44
Study Start Date: November 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
12-24 patients will be enrolled in the phase I component. 10 additional patients with NSCLC and 10 additional patients with HNCA will be treated at the Phase I expansion dose.
Drug: LBH589

One treatment cycle will be defined as a 21 day course of erlotinib with a total of 4 doses of LBH589 given biweekly on Tuesday and Friday for 1 week off and 2 weeks on (Days 9, 12, 16, and 19).

Patients may continue treatment with oral LBH589 until they experience unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator.

Drug: erlotinib

One treatment cycle will be defined as a 21 day course of erlotinib with a total of 4 doses of LBH589 given biweekly on Tuesday and Friday for 1 week off and 2 weeks on (Days 9, 12, 16, and 19).

Patients may continue treatment with oral LBH589 until they experience unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator.


Detailed Description:

Patients will be asked to remain on the study for a minimum of 3 months unless the study doctor decides the patient should be taken off the study or the patient withdraws from the study. Each cycle of treatment is 21 days in length and there is a 30 day follow-up after the patient receives their last dose of study drug. Scans will be repeated to see how their cancer is doing after two cycles of treatment. These scans wil be repeated every 2 cycles for the first six cycles and then every 3 cycles for as long as the patient remains on the study. The patient may continue on therapy as long as they are responding or have stable disease.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically documented diagnosis of advanced/metastatic NSCLC or Head and Neck cancer.
  • Male or female patients aged ≥ 18 years old
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Have progressive and measurable disease that can be measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Patients must have discontinued prior systemic chemotherapy by 14 days.
  • Patients must meet the following laboratory criteria:

    1. Serum albumin > 3g/dL
    2. AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) ) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement
    3. Serum bilirubin ≤ 1.5 x ULN
    4. Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
    5. Serum potassium ≥ LLN
    6. Serum phosphorous ≥ LLN
    7. Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
    8. Serum magnesium ≥ LLN
    9. TSH and free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
  • ECOG Performance Status of ≤ 1
  • Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
  • Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of LBH589 therapy due to risk of hypocalcemia.

Exclusion Criteria:

  • Impaired cardiac function including any one of the following:

    1. Screening ECG with a QTc > 450 msec confirmed by central laboratory prior to enrollment to the study
    2. Patients with congenital long QT syndrome
    3. History of sustained ventricular tachycardia
    4. Any history of ventricular fibrillation or torsades de pointes
    5. Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
    6. Patients with a myocardial infarction or unstable angina within 6 months of study entry
    7. Congestive heart failure (NY Heart Association class III or IV)
    8. Right bundle branch block and left anterior hemiblock (bifasicular block)
    9. Patients with a history of uncontrolled or chronic atrial fibrillation.
  • Uncontrolled hypertension, BP >180/110 on three separate occasions despite oral antihypertensive medications.
  • Concomitant use of drugs with a risk of causing torsades de pointes Concomitant use of CYP3A4 inhibitors.
  • Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
  • Patients with unresolved diarrhea > CTCAE grade 1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
  • Other concurrent severe and/or uncontrolled medical conditions
  • Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
  • Concomitant use of any anti-cancer therapy (except erlotinib) or radiation therapy.
  • Female patients who are pregnant or breast feeding or patients of reproductive potential not using two effective methods of birth control. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
  • Male patients whose sexual partners are WOCBP not using effective birth control
  • Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00738751

Contacts
Contact: Jill McHale 813-745-8384 jill.mchale@moffitt.org

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Leticia Tetteh     813-745-4617     leticia.tetteh@moffitt.org    
Contact: Anne Dellaportas     813-745-4616     anne.dellaportas@moffitt.org    
Principal Investigator: Janelle Gray, M.D.            
Principal Investigator: Eric Haura, M.D.            
Sub-Investigator: Soner Altiok, M.D., Ph.D.            
Sub-Investigator: Scott Antonia, M.D.            
Sub-Investigator: Gerald Bepler, M.D., Ph.D.            
Sub-Investigator: Alberto Chiappori, M.D.            
Principal Investigator: Ronald DeConti, M.D.            
Sub-Investigator: Sharon Litschauer, ARNP            
Sub-Investigator: Richard Lush, Ph.D.            
Sub-Investigator: Michelle Mintz, ARNP            
Sub-Investigator: George Simon, M.D.            
Sub-Investigator: Tawee Tanvetyanon, M.D.            
Sub-Investigator: Charles Williams, M.D.            
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Genentech
Novartis
Investigators
Principal Investigator: Jhanelle Gray, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Moffitt Cancer Center Clinical Trials website  This link exits the ClinicalTrials.gov site

Responsible Party: H. Lee Moffitt Cancer Center & Research Institute ( Jhanelle Gray, M.D. )
Study ID Numbers: MCC-15461, IND 102483, LBH589
Study First Received: August 18, 2008
Last Updated: December 1, 2008
ClinicalTrials.gov Identifier: NCT00738751  
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
NSCLC
Metastatic
erlotinib
aerodigestive tract cancers
non-small cell lung cancer
H&N cancer

Study placed in the following topic categories:
Erlotinib
Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Head and Neck Neoplasms
Carcinoma, Non-Small-Cell Lung

Additional relevant MeSH terms:
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009