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Phase I/II Clinical Trial Combining FUS1-nanoparticles and Erlotinib in Stage IV Lung Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Lung Cancer

Thank you

Trial Information

Phase I/II Clinical Trial Combining FUS1-nanoparticles and Erlotinib in Stage IV Lung Cancer

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of DOTAP:Chol-fus1 and erlotinib hydrochloride based on when you join this study. Up
to 4 dose levels of the study drug combination will be tested. Three (3) participants will
be enrolled at each dose level. The first group of participants will receive the first dose
combination level. After this dose is given, the participants will be watched for 3 weeks
to check for any serious side effects at that dose level. If any participants in this first
group have intolerable side effects, 1-2 lower dose combinations of the study drugs may be

If no intolerable side effects are seen in the first group, the second study group will
receive the next planned dose combination. If no intolerable side effects are seen in this
group, the last dose combination will be tested.

If you are enrolled in the Phase II portion, you will receive the highest study combination
dose that was tolerated in the Phase I portion.

During the Phase II portion of the study, half of the participants will not start receiving
erlotinib hydrochloride until Day 8 of Cycle 1 (+/- 1 day). Every odd-numbered participant
(1, 3, 5, and so on) enrolled in Phase II will receive this delayed schedule for erlotinib

Study Drug Administration:

You will receive the drugs dexamethasone and diphenhydramine before each infusion of
DOTAP:Chol-fus1, to try to lower the risk of possible allergic reactions to the study drug.
Dexamethasone will be given by mouth about 24 hours before your dose of DOTAP:Chol-fus1, and
by vein about 30 minutes before the dose. Diphenhydramine will also be given (either by
mouth or as an injection) about 30 minutes before the dose.

DOTAP:Chol-fus1 is given by vein as an infusion over 25-35 minutes, on Day 1 of every 3-week
study cycle.

You will take erlotinib hydrochloride by mouth in tablet form every day you are on study
(except for first week of Cycle 1, if you are enrolled in the Phase II delayed-schedule

Erlotinib hydrochloride tablets should be taken at about the same time each day. Each
erlotinib dose should be taken with about 8 ounces of water, and should be taken 1 hour
before or 2 hours after meals. The whole dose must be taken at one time. If you vomit
after taking the tablet(s), you should only re-take the dose if the tablet(s) can still be
seen and counted.

Study Tests:

Each study cycle is 3 weeks.

On Day 1 of each cycle:

- Your vital signs (blood pressure, heart rate, temperature, and breathing rate) will be

- Urine will be collected for routine tests.

- You will have a test to measure the level of oxygen in your blood.

On Day 1 of Cycle 1 only, blood (about 4 tablespoons total) will be drawn before your first
dose of DOTAP:Chol-fus1 and then about 24 hours later (+/- 4 hours), for research tests to
check your immune system.

On Day 2 of each cycle:

- Blood (about 2 teaspoons) will be drawn for routine tests and tests to check your
immune system.

- Your vital signs will be recorded, and you will be asked about any side effects you may

On Day 7 of Cycle 1, you will have a tumor biopsy for genetic research tests.

On Day 21 of each cycle:

- You will have a physical exam, including measurement of your vital signs.

- Your medical history will be recorded, and you will be asked about any side effects you
may be having.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

On Day 21 of every other cycle (Cycles 2, 4, 6, and so on), you will have either a chest CT
or PET/CT scan to check the status of the disease. Other scans may be performed, if your
doctor thinks they are needed.

PK Testing:

If you are in Phase 1 and are one of the first 6 participants to be enrolled on this study,
blood (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug in the body at different time points. PK samples
will be drawn during Cycle 1, at the following times:

- Day 1--before the dose of DOTAP:Chol-fus1, at 15 and 30 minutes after the dose, and
then 1, 3, and 6 hours after the dose

- Day 2

- Day 4

- Day 8

- Day 15

Length of Treatment:

You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse,
intolerable side effects occur, or you are unable to follow study directions.

End-of-Treatment Visit:

About 3 weeks after your last dose of DOTAP:Chol-fus1, you will be asked to return to the
clinic for an end-of-treatment visit.

- You will have a physical exam, including measurement of your vital signs.

- Your medical history will be recorded, and you will be asked about any side effects you
may be having.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- You will have either a chest CT or PET/CT scan to check the status of the disease.

Long-Term Follow-up:

You will be called by the study staff every 3 months after you stop taking the study drugs.
The study staff will ask you questions to find out how you are doing and to collect
information on any other therapies you have received for cancer. The call should take about
15 minutes.

This is an investigational study. Erlotinib hydrochloride is commercially available and FDA
approved for the treatment of non-small-cell lung cancer. At this time, DOTAP:Chol-fus1 is
only being used in research.

Up to 57 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

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

2. Stage IV NSCLC, or recurrent NSCLC that is not potentially curable by radiotherapy or
surgery whether or not they have received prior chemotherapy. There is no limit to
the number of prior chemotherapy regimens received.

3. All patients must have tumor specimens adequate for analysis of EGFR mutations and
have tumor accessible to biopsy and must consent to biopsy.

4. Karnofsky Performance Status of 70% or greater, or Zubrod Performance Status of 1or

5. Age >/= 18 years.

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

7. Negative serum pregnancy test (serum HCG) within 7 days of study treatment if female
and of childbearing potential (non-childbearing is defined as greater than one year
post-menopausal surgically sterilized). 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 along with 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.

8. Subjects are required to agree to practice effective birth control (i.e. abstinence,
intrauterine device for female subjects) during the study period.

9. Patients must be 4 weeks or greater, beyond major surgical procedures such as
thoracotomy, laparotomy or joint replacement, and must be 1.5 weeks or greater,
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.

10. ANC > 1500/mm3, plt count > 100,000/mm3

11. PT and PTT < 1.25 times the institutional upper limit of normal.

12. Adequate renal function documented by serum creatinine of 1.5 mg/dl or less, or
calculated creatinine clearance > 50 ml/min.

13. Adequate hepatic function as documented by serum bilirubin< 1.5 mg/dl and SGOT and
SGPT 1.5 or less x upper limit of normal.

14. 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 >/= 4 weeks 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.

15. Stable cardiac condition with a left ventricular ejection fraction of 40% or greater.

16. FEV1 and corrected DLCO of 35% or > of predicted.

17. Absence of an activating mutation (Exon 19 deletion or Exon 21 L858R mutation) in the
epidermal growth factor receptor (EGFR) in the pre-treatment biopsy of the tumor.
Patients with activating EGFR mutations are eligible if they have progressed
following treatment with erlotinib. A pretreatment tumor biopsy must be available for
analysis. If a biopsy has not been performed prior to entry, then a biopsy will be

Exclusion Criteria:

1. Females who are pregnant or breast-feeding.

2. "Study entry" is defined as the date of informed consent. Patients who received
investigational therapy (agents that are not FDA approved), 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 who have received standard chemotherapy with FDA approved agents within 21
days of entry into the protocol.

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

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

6. Patients with brain metastases (except as allowed in section 4.1.13) of the protocol.
Neurological assessment will be used to determine brain metastases.

7. 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

8. Prior gene therapy.

9. History of myocardial infarction within 6 months or unstable angina within the past 6

10. Patients known to be HIV positive are ineligible.

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 (MTD) Level for Drug Treatment Combination

Outcome Description:

MTD defined as dose level at which less than 2 participants experience dose-limiting toxicity (DLT). Toxicity graded according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4. DLT will be grade > 3 toxicity occurring during the first cycle of therapy (i.e., within the first 3 weeks).

Outcome Time Frame:

First 21 day cycle

Safety Issue:


Principal Investigator

Charles Lu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2013

Completion Date:

Related Keywords:

  • Lung Cancer
  • Lung Cancer
  • Non-small cell lung cancer
  • FUS1-nanoparticles
  • DOTAP:Chol-fus1
  • DOTAP:Cholesterol-Fus1 Liposome Complex
  • Erlotinib
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva
  • Dexamethasone
  • Decadron
  • Diphenhydramine
  • Benadryl
  • Benylin Cough SyrupPharmacokinetic
  • PK
  • Lung Neoplasms



UT MD Anderson Cancer CenterHouston, Texas  77030