Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers

NCT00738751 | Completed Phase 1

• 2 other identifiers: MCC-15461LBH589
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer; Head and Neck Cancer

Keywords

NSCLC; Metastatic; erlotinib; aerodigestive tract cancers; non-small cell lung cancer; H&N cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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.

  4 Months

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  Up to 48 months

• Progression Free Survival (PFS) by Cancer Type

  Up to 48 months

• Overall Survival (OS) by Cancer Type

  Up to 48 months

Study Arms (1)

Dose Escalation Followed by Expansion

EXPERIMENTAL

Eligible participants were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of twice weekly panobinostat plus daily erlotinib at 4 planned dose levels (DLs).

Drug: Panobinostat (LBH589); Drug: erlotinib

Interventions

Panobinostat (LBH589) DRUG

Panobinostat was taken twice weekly, for 2 out of 3 weeks of each cycle. Each cycle was defined as a 21-day period. Four dose levels of panobinostat in combination with erlotinib were planned: 1) dose level 1 (DL1) = panobinostat 20 mg by mouth (PO) twice weekly for 2 out of 3 weeks + erlotinib 100 mg PO daily; 2) dose level 2 (DL2) = panobinostat 30 mg and erlotinib 100 mg; 3) dose level 3 (DL3) = panobinostat 30 mg and erlotinib 150 mg; and 4) dose level 4 (DL4) = panobinostat 40 mg and erlotinib 150 mg. Doses were not escalated over the course of treatment of an individual participant.

Also known as: histone deacetylase inhibitor, HDAC

Dose Escalation Followed by Expansion

erlotinib DRUG

Erlotinib was taken daily without interruption. Each cycle was defined as a 21-day period. Panobinostat was taken twice weekly, for 2 out of 3 weeks of each cycle. Four dose levels of panobinostat in combination with erlotinib were planned: 1) dose level 1 (DL1) = panobinostat 20 mg by mouth (PO) twice weekly for 2 out of 3 weeks + erlotinib 100 mg PO daily; 2) dose level 2 (DL2) = panobinostat 30 mg and erlotinib 100 mg; 3) dose level 3 (DL3) = panobinostat 30 mg and erlotinib 150 mg; and 4) dose level 4 (DL4) = panobinostat 40 mg and erlotinib 150 mg. Doses were not escalated over the course of treatment of an individual participant.

Also known as: Tarceva, quinazoline

Dose Escalation Followed by Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Genentech, Inc.: collaborator
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Head and Neck Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung

Interventions

Panobinostat; Histone Deacetylase Inhibitors; Erlotinib Hydrochloride; Quinazolines

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Jhanelle Gray, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2008
• First Posted: August 20, 2008
• Study Start: November 1, 2008
• Primary Completion: August 1, 2013
• Study Completion: February 1, 2015
• Last Updated: February 4, 2015

Record last verified: 2015-02

Locations

US (1)