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

Non-Small Cell Lung Cancer Clinical Trial

Official title: Pemetrexed and LBH589 in Previously-Treated Patients With Advanced Non-Small Cell Lung Cancer

Status Terminated

Clinical Trial 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.

Clinical Trial Description

Objectives

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).

2. To 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).

3. To determine the pharmacodynamic effects of LBH589 and pemetrexed on levels of histone deacetylase (HDAC) 1 and 6 in peripheral blood mononuclear cells, as well as on levels of vascular endothelial growth factor (VEGF) levels in the blood.

4. To identify biomarkers in baseline, archival tumor tissue that may correlate with antitumor efficacy.

Subject population Phase I: We will enroll patients treated with any number of prior regimen and all thoracic malignancies, except squamous cell carcinoma of the lung.

Phase II: We will enroll patients with recurrent or progressive NSCLC who have received 1 prior chemotherapy regimen (1 additional regimen in the setting of initial curative treatment is allowed if completed >1 year earlier).

Treatment plan

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

• 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 pharmacodynamic (PD) studies will be performed (week -1)

Study design and sample size:

This is a phase I/II study. Phase I: 9-18 patients (estimated); Phase II: 17-41 patients (estimated). ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

• NCT number: NCT00907179
• Study type: Interventional
• Source: University of Pittsburgh
• Status: Terminated
• Phase: Phase 1
• Start date: July 2009
• Completion date: July 2015