Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers
Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers
The main purpose of the study is to:

 -  Determine the safety and tolerability of erlotinib and LBH589B.

 -  Establish a recommended phase II expansion dosing of LBH589B and erlotinib in patients
 with advanced aerodigestive tract cancers.
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. Aspartic transaminase (AST/SGOT) and alanine transaminase (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 ≥ lower limit of normal (LLN) and ≤ ULN

 6. Serum phosphorous ≥ LLN

 7. Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN

 8. Serum magnesium ≥ LLN

 9. Absolute neutrophil count (ANC) (ANC: segmented and bands) ≥ 1.5 X10^9/L

 10. Platelets ≥ 100 X 10^9/L

 -  Baseline multiple gated acquisition imaging (MUGA) or echocardiogram (ECHO) must
 demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the
 institutional normal

 -  Eastern Cooperative Oncology Group (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 instructed that intravenous (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 electrocardiogram (ECG) with a corrected QT (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 - New York Heart Association (NYHA) class III or IV

 8. Right bundle branch block and left anterior hemiblock (bifascicular block)

 9. Patients with a history of uncontrolled or chronic atrial fibrillation.

 -  Uncontrolled hypertension, blood pressure (BP) >180/110 on 3 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 > Common Terminology Criteria for Adverse Events
 (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 < 14 days, any investigational drug < 14 days
 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

 -  Patients who are not willing to refrain from wearing contact lenses during study
 participation will be excluded.