Phase I Study of LBH589 & Erlotinib for 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:

Serum albumin ≥ 3g/dL
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
Serum bilirubin ≤ 1.5 x ULN
Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
Serum potassium ≥ lower limit of normal (LLN) and ≤ ULN
Serum phosphorous ≥ LLN
Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
Serum magnesium ≥ LLN
Absolute neutrophil count (ANC) (ANC: segmented and bands) ≥ 1.5 X10^9/L
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:

Screening electrocardiogram (ECG) with a corrected QT (QTc) > 450 msec confirmed by central laboratory prior to enrollment to the study
Patients with congenital long QT syndrome
History of sustained ventricular tachycardia
Any history of ventricular fibrillation or torsades de pointes
Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
Patients with a myocardial infarction or unstable angina within 6 months of study entry
Congestive heart failure - New York Heart Association (NYHA) class III or IV
Right bundle branch block and left anterior hemiblock (bifascicular block)
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.