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: TUSC2-nanoparticles and Erlotinib in Stage IV Lung Cancer
  • Official Title: Phase I/II Clinical Trial Combining TUSC2-nanoparticles and Erlotinib in Stage IV Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: GEN-102
  • NCT ID: NCT01455389

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
DOTAP:Chol-TUSC2DOTAP:Cholesterol-TUSC2 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-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.

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-TUSC2 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. NOTE: For all participants dosing of erlotinib has been changed to begin on
      Day 8 of Cycle 1 and then daily.

      Study Drug Administration:

      You will receive the drugs dexamethasone and diphenhydramine before each infusion of
      DOTAP:Chol-TUSC2, 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-TUSC2, 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-TUSC2 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 were 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-TUSC2 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 liquid 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-TUSC2, 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-TUSC2 is
      only being used in research.

      Up to 57 patients will take part in this study. All will be enrolled at MD Anderson as well
      as additional clinical sites.
    

Trial Arms

NameTypeDescriptionInterventions
DOTAP + ErlotinibExperimentalDOTAP:Chol-TUSC2 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-TUSC2
  • 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. There is no limit to the number or form of prior therapy regimens received,
             but patients must have received at least one.

          3. All subjects must have tumor specimens adequate for analysis of EGFR mutations or have
             tumor accessible for pretreatment biopsy, and must consent to post-treatment Guardant
             ctDNA liquid biopsy. Subjects must have specimens adequate for analysis of EGFR
             mutations (and other clinically relevant biomarkers)

          4. All subjects with an activating EGFR mutation (exon 19 deletion or exon 21 L858R
             mutation) are eligible IF they have progressed following treatment with a first,
             second, or third generation EGFR inhibitor. All subjects who are EGFR negative or have
             wild-type EGFR or another non-activating mutation are eligible.

          5. ECOG or Zubrod Performance Status ≤1

          6. Age ≥18 years

          7. Subjects must have voluntarily signed an informed consent in accordance with
             institutional policies.

          8. Female subjects of childbearing potential (non-childbearing is defined as greater than
             one year post-menopausal or surgically sterilized) must have a Negative serum
             pregnancy test (serum beta-HCG) ≤7 days of study treatment. 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 (2)
             Transvaginal Ultrasound (TVUS) scans one (1) week apart along with serial beta-HCG
             levels two (2) 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.

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

         10. Subjects 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. Note: placement of pleurex catheter is not considered
             minor surgery for this study.

         11. ANC >1500/mm3, platelet count >100,000/mm3 ≤14 days of study treatment

         12. PT and PTT <1.25 times the institutional upper limit of normal ≤14 days of study
             treatment

         13. Adequate renal function documented by serum creatinine of ≤1.5 mg/dl or calculated
             creatinine clearance >50 ml/min ≤14 days of study treatment

         14. Adequate hepatic function as documented by serum bilirubin <1.5 mg/dl and SGOT and
             SGPT ≤2.5 X upper limit of normal ≤14 days of study treatment

         15. Subjects 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 start of study
             treatment. Subjects must be off steroids that were being administered because of brain
             metastases or related symptoms for ≥2 weeks prior to start of study treatment.
             Post-treatment imaging ≤2 weeks of informed consent must demonstrate stability or
             regression of the brain metastases.

         16. Stable cardiac condition with a left ventricular ejection fraction ≥40% ≤28 days of
             study treatment

        Exclusion Criteria:

          1. Subject is female who is pregnant or breast-feeding.

          2. Subject received investigational therapy (i.e., agents that are not FDA-approved),
             including monoclonal antibodies such as bevacizumab or cetuximab, or has received
             radiotherapy to the skull, spine, thorax or pelvis within ≤30 days of start of study
             treatment. Subjects are permitted to have received palliative radiotherapy to an
             extremity provided ≥14 days have elapsed since completion of radiotherapy, provided
             the subject received ≤10 radiotherapy fractions and a dose ≤30 Gy to that site, and
             provided skull, spine, thorax or pelvis were not in the radiotherapy field.

          3. Subject received standard chemotherapy with FDA-approved agents within ≤21 days of
             start of study treatment.

          4. Subject received a targeted therapy within ≤14 days prior to start of study treatment.

          5. Subject has active systemic viral, bacterial or fungal infection(s) requiring
             treatment.

          6. Subject has brain metastases (except as allowed in Section 3.2.1). Neurological
             assessment will be used to determine brain metastases.

          7. Subject has 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. Subject received prior gene therapy or cell therapy.

          9. Subject has history of myocardial infarction or unstable angina ≤6 months of start of
             study treatment.

         10. Subject is known to be HIV positive.
      
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:Active, not recruiting
Lead Sponsor:Genprex, Inc.

Trial Keywords

  • Lung Cancer
  • Non-small cell lung cancer
  • NSCLC
  • FUS1-nanoparticles
  • DOTAP:Chol-TUSC2
  • DOTAP:Cholesterol-TUSC2 Liposome Complex
  • Erlotinib
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva
  • Dexamethasone
  • Decadron
  • Diphenhydramine
  • Benadryl
  • Benylin Cough SyrupPharmacokinetic
  • PK

Last Updated

July 22, 2020