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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

Phase 1
Not Enrolling
Lung Cancer

Thank you

Trial Information

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.

Inclusion Criteria:

1. Histologically or cytologically documented non-small cell lung cancer (NSCLC) or
small cell lung cancer (SCLC)

2. For NSCLC subjects: Locally advanced, unresectable, incurable stage IIIB (pleural
effusion) or stage IV NSCLC, or recurrent NSCLC that is not potentially curable by
radiotherapy or surgery. Patients must have received at least one prior
platinum-based chemotherapy regimen for NSCLC. For SCLC subjects: Extensive disease
or recurrent disease after initial treatment for limited disease. Patients must have
received prior platinum-based chemotherapy or chemoradiotherapy. All subjects: There
is no limit to the number of prior chemotherapy regimens received.

3. Preference will be given to patients with tumors amenable to biopsy. In the expansion
cohort at MTD, all patients must have tumor amenable to biopsy and must consent to

4. Karnofsky Performance Status >= 70%, or Zubrod Performance Status <= 1.

5. Negative serum pregnancy test (serum HCG) if female and of childbearing potential.
Since beta-HCG may be falsely elevated as a result of malignancy, women of
child-bearing potential who have an elevated serum beta-HCG level are eligible for
enrollment if they have two Transvaginal Ultrasound (TVUS) scans one week apart and
serial beta-HCG levels two weeks apart that are inconsistent with pregnancy and a
Gynecology consult to ensure that the beta- HCG level was at a value high enough to
see pregnancy with TVUS. Subjects must agree to practice effective birth control
during the study period.

6. Negative serology for Human Immunodeficiency Virus.

7. Patients must be >/= 4 weeks beyond major surgical procedures such as thoracotomy,
laparotomy or joint replacement, and must be >/= 1.5 weeks beyond minor surgical
procedures such as biopsy of subcutaneous tumors, pleuroscopy, etc, and must not have
evidence of wound dehiscence, active wound infection, or comparable major residual
complications of the surgery. Absolute neutrophil count (ANC) > 1500 * 10**9/mm**3,
platelet count > 100,000 * 10**9/mm**3. Prothrombin time (PT) and Partial
thromboplastin time (PTT) < 1.25 times the institutional upper limit of normal.

8. Adequate renal function documented by serum creatinine of <= 1.5 mg/dl or calculated
creatinine clearance > 50 ml/min.

9. Adequate hepatic function as documented by serum bilirubin< 1.5 mg/dl and SGOT and
10. FEV1 and corrected DLCO of >/= 40% of predicted.

11. Patients with asymptomatic brain metastases that have been treated are eligible if
the following criteria are met: No history of seizures in the preceding 6 months.
Definitive treatment must have been completed ≥4weeks prior to registration. Subjects
must be off steroids that were being administered because of brain metastases or
related symptoms for ≥2 weeks. Post-treatment imaging within 2 weeks of registration
must demonstrate stability or regression of the brain metastases.

12. Stable cardiac condition with a left ventricular ejection fraction > 50%.

13. Patients must have voluntarily signed an informed consent in accordance with
institutional policies.

Exclusion Criteria:

1. Females who are pregnant or breast-feeding.

2. Patients who received investigational therapy, monoclonal antibody such as
bevacizumab or cetuximab, or who received radiotherapy to the skull, spine, thorax or
pelvis within 30 days of entry into the protocol. Patients are permitted to have
received palliative radiotherapy to an extremity provided at least 14 days has
elapsed since completion of therapy, provided the patient received no more than 10
radiotherapy fractions and a dose no higher than 30 Gy to that site, and provided
skull, spine, thorax or pelvis were not in the radiotherapy field.

3. Patients with brain metastases (except as allowed in inclusion criterion #11).
Neurological assessment will be used to determine brain metastases.

4. Active systemic viral, bacterial or fungal infections requiring treatment.

5. Patients with serious concurrent illness or psychological, familial, sociological,
geographical, or other concomitant conditions that, in the opinion of the
investigator, would not permit adequate follow-up and compliance with the study

6. Use of any investigational agent within four weeks of study treatment.

7. Prior gene therapy.

8. History of myocardial infarction within 6 months, angina within the past 6 months, or
a history of arrhythmias on active therapy.

9. Patients who have received standard chemotherapy with FDA approved agents within 21
days of entry into the protocol.

10. Patients who have received therapy with an oral tyrosine kinase inhibitor (eg,
erlotinib) within 14 days prior to entry into the protocol.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose of DOTAP:Chol-fus1

Outcome 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.

Safety Issue:


Principal Investigator

David J. Stewart, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2003

Completion Date:

April 2011

Related Keywords:

  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Lung Cancer
  • SCLC
  • DOTAP:Chol-fus1
  • gene
  • gene transfer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



University of Texas M.D. Anderson Cancer Center Houston, Texas  77030