Clinical Trials /

TUSC2-nanoparticles and Erlotinib in Stage IV Lung Cancer

NCT01455389

Description:

The goal of phase 1 of this clinical research study is to find the highest dose of DOTAP:Chol-TUSC2 that can be safely given in combination with Tarceva (erlotinib hydrochloride) to patients with NSCLC. The goal of phase 2 of this clinical research study is to learn if the combination of DOTAP:Chol-TUSC2 and erlotinib hydrochloride can help to control NSCLC. The safety of this drug combination will also be studied in both phases. DOTAP:Chol-TUSC2 (previously FUS1) is a drug that helps transfer a gene called TUSC2 into cancer cells. Researchers think that cells without this gene may be involved in the development of lung cancer tumors. They want to find out if replacing the gene in these cells may keep the tissue from forming cancer cells. Erlotinib hydrochloride is designed to block a protein on tumor cells that may control tumor growth and survival. This may stop tumors from growing.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FUS1-nanoparticles and Erlotinib in Stage IV Lung Cancer
  • Official Title: Phase I/II Clinical Trial Combining FUS1-nanoparticles and Erlotinib in Stage IV Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2011-0432
  • NCT ID: NCT01455389

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
DOTAP:Chol-fus1DOTAP:Cholesterol-Fus1 Liposome ComplexDOTAP + Erlotinib
ErlotinibErlotinib Hydrochloride, OSI-774, TarcevaDOTAP + Erlotinib
DexamethasoneDecadronDOTAP + Erlotinib
DiphenhydramineBenadryl, Benylin Cough Syrup [OTC]DOTAP + Erlotinib

Purpose

The goal of phase 1 of this clinical research study is to find the highest dose of DOTAP:Chol-fus1 that can be safely given in combination with Tarceva (erlotinib hydrochloride) to patients with NSCLC. The goal of phase 2 of this clinical research study is to learn if the combination of DOTAP:Chol-fus1 and erlotinib hydrochloride can help to control NSCLC. The safety of this drug combination will also be studied in both phases. DOTAP:Chol-fus1 is a drug that helps transfer a gene called fus1 into cancer cells. Researchers think that cells without this gene may be involved in the development of lung cancer tumors. They want to find out if replacing the gene in these cells may keep the tissue from forming cancer cells. Erlotinib hydrochloride is designed to block a protein on tumor cells that may control tumor growth and survival. This may stop tumors from growing.

Detailed Description

      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
      tested.

      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
      hydrochloride.

      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
      group).

      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
           measured.

        -  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
           have.

      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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
DOTAP + ErlotinibExperimentalDOTAP:Chol-fus1 0.045 mg/kg by vein over 25-35 minutes on day 1 of each 21 day cycle; and Erlotinib 100 mg by mouth daily for each 21 day cycle.
  • DOTAP:Chol-fus1
  • Erlotinib
  • Dexamethasone
  • Diphenhydramine

Eligibility Criteria

        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
             less.

          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 required.

        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 4.1.14 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
             protocol.

          8. Prior gene therapy.

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

         10. Patients known to be HIV positive are ineligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) Level for Drug Treatment Combination
Time Frame:First 21 day cycle
Safety Issue:
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).

Secondary Outcome Measures

Measure:Response Rate
Time Frame:After two, 21 day cycles
Safety Issue:
Description:Responses determined by RECIST criteria. Responses will include only complete response (CR) + partial response (PR). Participants considered as non-responders when tumor progression by RECIST is observed. Measurable disease is defined as tumor masses with identifiable diameters measurable in two dimensions by computed tomography. Best overall response is best response designation recorded from the start of treatment until disease progression. Complete and partial responses have to be confirmed by two evaluations of the disease taken at least four weeks apart.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genprex, Inc.

Trial Keywords

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

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