Pemetrexed and LBH589 in Patients With Advanced Non-Small Cell Lung Cancer

NCT00907179 | Terminated Phase 1 DMC

• 1 other identifier: 08-036
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

LBH589 is a drug that may slow down the growth of cancer cells or kill cancer cells by blocking certain enzymes. LBH589 has shown effects against cancer in laboratory studies and in studies using animals; however, it is not known if this medicine will show the same activity in humans. As of May 2006, approximately 100 patients have received treatment with either an intravenous or capsule form of LBH589. Only the capsule form of LBH589 will be used in this study. In addition, information from other research studies and laboratory studies suggests that this study drug may help to treat lung cancer. The main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with pemetrexed in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how the patient's lung cancer responds to the LBH589 in combination with pemetrexed. This study will also investigate how the patient's body processes the combination of LBH589 and pemetrexed. To determine this, the investigators will measure the amount of study drug in the patient's blood. This will be done with a series of blood tests, called pharmacokinetic (PK) tests. Other purposes of this study will be to determine the side effects of LBH589 in combination with pemetrexed and whether or not this combination is effective in treating your type of cancer.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose of LBH589 given on a three times weekly schedule when combined with pemetrexed for the treatment of patients with advanced thoracic malignancies, except squamous cell carcinoma of the lung (phase I part)

  6 months

Secondary Outcomes (3)

• Determine the overall response rate and non-progression rate (clinical benefit rate) and progression-free survival of the combination of LBH589 and pemetrexed in patients with previously-treated advanced NSCLC (phase II part).

  1 year

• Determine the pharmacodynamic effects of LBH589 and pemetrexed on levels of HDAC 1 and 6 in peripheral blood mononuclear cells, as well as on levels of VEGF levels in the blood.

  1 year

• Identify biomarkers in baseline, archival tumor tissue that may correlate with antitumor efficacy.

  1 year

Study Arms (1)

Dose escalation

EXPERIMENTAL

Phase I: Determine the highest and safest dosage of LBH589 (15 mg, 20 mg, and 30 mg). If the 15 mg dosage causes too many side effects, a back-up dosage of 10 mg will be used instead of the 15 mg. Pemetrexed 500mg/m2 IV, day 1, every 21 days, on the first day of the week LBH589 is given

Drug: LBH 589; Drug: Pemetrexed

Interventions

LBH 589 DRUG

LBH589 three-times-a-week (doses will be at least 2 days apart, e.g. Monday, Wednesday, Friday), until disease progression or intolerable toxicities LBH589 will start the week prior to the first pemetrexed cycle and PD studies will be performed (week -1). Dose level: 1 LBH589: 10 mg Pemetrexed: 500 mg/m2 Dose level: 2 LBH589: 15 mg Pemetrexed: 500 mg/m2 Dose level: 3 LBH589: 20 mg Pemetrexed: 500 mg/m2 Dose level: 4 LBH589: 30 mg Pemetrexed: 500 mg/m2

Also known as: Panobinstat

Dose escalation

Pemetrexed DRUG

Pemetrexed 500mg/m2 IV, day 1, every 21 days, on the first day of the week LBH589 is given.

Also known as: Alimta

Dose escalation

Eligibility Criteria

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

You may qualify if:

• Phase I only: any number of prior regimens is allowed and all thoracic malignancies, except squamous cell carcinoma of the lung.
• Phase II only: Patients with recurrent or progressive advanced stage non-squamous cell NSCLC (no small cell lung cancer/SCLC component) who have received 1 prior chemotherapy regimen for advanced NSCLC. Chemotherapy as part of initially potentially curative therapy that was completed \<1 year counts as 1 prior regimen. Prior erlotinib or one other biologic regimen is also allowed.
• Measurable disease (RECIST) (for phase II part only)
• Patients may not have received prior pemetrexed or histone deacetylase inhibitor (HDACi) therapy, including valproic acid, for the treatment of any medical condition.
• ECOG (Eastern Cooperative Oncology Group) Performance Status of ≤ 2
• Aged ≥ 18 years old and ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must meet the following laboratory criteria:
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1500/mm³
• Platelets ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Biochemistry:
• Total Bilirubin within normal institutional limits.
• Aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN)
• Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula

You may not qualify if:

• Prior HDAC, deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
• Impaired cardiac function including any one of the following:
• Screening ECG with a 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 (NY Heart Association class III or IV)
• Right bundle branch block and left anterior hemiblock (bifascicular block)
• Uncontrolled hypertension. Patients with history of hypertension must be well-controlled (≤150/100) on a stable regimen of anti-hypertensive therapy.
• Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
• Concomitant use of Cytochrome (CYP3A4) inhibitors (See Appendix 1-2) is not allowed. The use of cytochrome (CYP2D6) substrates (Appendix 1, table 0-3) should be done with caution. If drugs that are CYP2D6 substrates arte to be continued, patients should be carefully monitored and may require dose titration or dose reduction of the CYP2D6 substrate.
• Patients with unresolved diarrhea \> CTCAE (NCI common terminology criteria for adverse events ) grade 1

Sponsors & Collaborators

• University of Pittsburgh: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Panobinostat; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Ahmad Tarhini, MD

  University of Pittsburgh

  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: May 20, 2009
• First Posted: May 22, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 22, 2015

Record last verified: 2015-07

Locations

US (1)