Study to Determine the Maximum Tolerated Dose of LErafAON in Patients With Advanced Cancer
The primary purpose of this study is to identify a dose of Liposome Entrapped c-raf Antisense Oligonucleotide Easy-to-Use (LErafAON-ETU) which maximizes potential benefits of the compound to patients with advanced cancer, without compromising their safety. This study will also assess the processing of LErafAON-ETU by the body over time. Patients will receive an intravenous infusion of LErafAON-ETU each week. Multiple blood samples will be taken for pharmacokinetic analysis during the first treatment; two samples will be taken during both the second and third treatments. Patients will be eligible to continue treatment until the occurrence of unacceptable toxicity or disease progression.
In LErafAON-ETU, antisense oligonucleotides specific to c-raf, are associated with liposomes, which are microscopic membrane-like structures created from lipids (fats). Raf-1 is a protein which plays a critical role in many aspects of cellular activation and growth. Therefore, it is thought to be an important factor that may support tumor development. LErafAON-ETU potentially limits the ability of a cell to produce the Raf-1 protein.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of an Easy-to-Use Intravenous Formulation of Liposome Entrapped C-raf Antisense Oligonucleotide (LErafAON-ETU) Administered on a Weekly Schedule in Patients With Advanced Cancer|
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of LErafAON-ETU.
- To determine the pharmacokinetics of raf antisense oligonucleotide after intravenous administration of LErafAON-ETU
- To determine any anti-tumor effects of LErafAON-ETU.
|Study Start Date:||December 2004|
|Study Completion Date:||November 2010|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
This Phase I, open-label, dose-escalation study is designed to determine the maximum tolerated dose of LErafAON-ETU in patients who have advanced cancer considered unresponsive to available, conventional modalities or treatments. LErafAON-ETU will be administered as an IV infusion once weekly for 3 consecutive weeks (a Treatment Cycle). A complete pharmacokinetic profile of raf-1 antisense oligonucleotide will be assessed in week 1 only; limited pharmacokinetic sampling will be done prior to and at the end of infusion in weeks 2 and 3 only. Tumor/disease evaluation will be performed upon completion of 6 infusions (2 Cycles). Dose escalation will not occur until the safety and tolerability at a given dose level has been confirmed for 1 Cycle.
|United States, Arizona|
|Scottsdale, Arizona, United States, 85260|
|United States, California|
|Premiere Oncology-Santa Monica|
|Santa Monica, California, United States, 90404|