Clinical trial NCT00738751: Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers
Official title: Phase I Study of LBH589 in Combination With Erlotinib for Advanced Aerodigestive Tract Cancers (CLBH5889CUS11T)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Head and Neck Cancer
Keywords: NSCLC
Metastatic
erlotinib
aerodigestive tract cancers
non-small cell lung cancer
H&N cancer
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Novartis
First posted: 2008-08-20
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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. 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 4 Months
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to 48 months
measure: Progression Free Survival (PFS) by Cancer Type
timeFrame: Up to 48 months
measure: Overall Survival (OS) by Cancer Type
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Jhanelle Gray, M.D.
role: PRINCIPAL_INVESTIGATOR
References: