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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose of DOTAP:Chol-fus1
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.
David J. Stewart, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|University of Texas M.D. Anderson Cancer Center||Houston, Texas 77030|