Phase I Study of IV DOTAP: Cholesterol-Fus1 in Non-Small-Cell Lung Cancer
The goal of this clinical research study is to find out the highest safe dose of DOTAP:Chol-fus1 that can be given to participants in the treatment of non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). This study is an attempt to transfer a gene (fus1) into cancer cells, using the drug DOTAP:Cholesterol-fus1. Researchers will also study the side effects of this experimental gene transfer at different doses, and will conduct tests to see if there are any effects on tumor size at different doses. Experimental transfer of the fus1 gene into humans has never been tried before.
- Assess the toxicity of DOTAP:Cholesterol-fus1 Liposome Complex (DOTAP:Chol-fus1) administered intravenously.
- To determine the maximal tolerated dose and recommended phase II dose of DOTAP:Chol-fus1 administered intravenously.
- Assess the expression of fus1 following intravenous delivery of DOTAP:Chol-fus1 in tumor and normal bronchial epithelial cell biopsies.
- Assess any anti-cancer activity for DOTAP:Chol-fus1.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study Of Intravenous DOTAP:Cholesterol-Fus1 Liposome Complex (DOTAP:Chol-fus1) In Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Previously Treated With Chemotherapy|
- Maximum Tolerated Dose of DOTAP:Chol-fus1 [ Time Frame: Before each dose level (3 weeks); Days 2, 3, and 8 after first dose, blood tests, vital signs, and side effects; and after every two treatment cycles or 6 weeks, tumor measured using CT or MRI scan. ] [ Designated as safety issue: Yes ]
- Toxicity of the Intravenous DOTAP:Chol-fus1 complex [ Time Frame: Observation for 2 weeks follwing each treatment cycle (3 weeks) for toxicity. ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2003|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Infusion intravenous once every 3 weeks
Infusion of DOTAP:Chol-fus1 by vein once every 3 weeks.
Other Name: DOTAP:Chol-FUS1 Liposomes
DOTAP:Chol-fus1 is a drug that helps transfer the fus1 gene into cancer cells. It is thought that the absence of the fus1 gene may be involved in the development of lung cancer tumors. The idea is to try to replace this gene in lung cancer cells.
Participants in this study must have advanced lung cancer that has worsened after receiving prior chemotherapy. Before treatment begins, participants will have a physical exam. Blood (about 2 tablespoons) and urine tests will be performed. Women able to have children will have a blood pregnancy test. Please note that it is possible that the tumor could cause a "positive" pregnancy test result, when you are not pregnant. If a pregnancy test comes back positive, and for any reason you and/or the research staff believes that this may be an error, additional tests may be done to confirm or rule out pregnancy. The participant's tumor will be measured using CT, PET/CT or MRI scans. Participants will also have an EKG (heart function test) and a MUGA scan or echocardiogram.
A treatment cycle on this study is 3 weeks. Participants will receive pre-medications of dexamethasone and diphenhydramine prior to the infusion of DOTAP:Chol-fus1 to try to lessen the potential reactions to the infusion. The participant will receive a short infusion of DOTAP:Chol-fus1 by vein once every 3 weeks. Participants will be examined by their doctor before each treatment. In addition, participants will return to the clinic on days 2, 3, and 8 after the first dose to have blood tests done, their vital signs checked, and to look for side effects. After every two treatment cycles or 6 weeks, the participant's tumor will be measured using a CT or MRI scan. Participants can continue to receive treatments until the tumor gets worse, side effects become too severe, or a maximum of 6 treatments have been given. Treatment may continue for participants who continue to benefit from the treatment at the end of the planned 6 treatments if the treating physician, the principle investigator, and an advisor from the FDA all agree. Participants will return to the clinic 3 weeks after their last dose of DOTAP:Chol-fus1 to have their vital signs checked and to look for side effects. After all treatments are finished, participants will be contacted every 3 months for an update on their health and to gather information about any other treatment(s) they have received.
Participants entered at a given dose level will not be able to receive a higher dose while on study. A group of 3 participants will receive DOTAP:Chol-fus1 by vein at each dose level. After treating 3 participants at a given dose level, the participants will be observed for 2 weeks to evaluate the toxicity. The information showing if the participants develop severe side effects, referred to as dose-limiting toxicity (DLT), will be recorded for computing the chance of toxicity. This information will be used to help select the dose level for the next group of participants. The goal is to find the dose level where 10% of participants develop severe side effects (dose-limiting toxicity).
All the participants will be treated in a dose-escalation fashion starting from the lowest level. The next dose level can be moved up if calculation of the side effects shows that a higher dose is needed. However, no skipping of doses is allowed.
This is an investigational study. Up to 51 individuals will receive study drug on this study. All will be enrolled at M. D. Anderson.
|United States, Texas|
|University of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||David J. Stewart, MD||M.D. Anderson Cancer Center|