Lung Cancer | TUSC2-nanoparticles and Erlotinib in Stage IV Lung Cancer

Lung Cancer research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Lung Cancer

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:DOTAP:Chol-TUSC2Starting Dose 0.045 mg/kg by vein on day 1 of each 21 day cycle; Phase II is Maximum Tolerated Dose from Phase I.

Drug:ErlotinibStarting Dose 100 mg by mouth each day of a 21 day cycle (except for first week of Cycle 1, if enrolled in Phase II delayed-schedule group). Phase II is Maximum Tolerated Dose from Phase I.

Drug:Dexamethasone8 mg orally 24 and 12 hours and 20 mg by vein 30 minutes before DOTAP:Chol-TUSC2 treatment followed by 8 mg orally at 12, 24 and 36 hours after treatment (total number doses = 5).

Drug:Diphenhydramine50 mg by mouth or by vein 30 minutes prior to treatment with DOTAP:Chol TUSC2

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

DOTAP + ErlotinibDOTAP: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.

Study Status

Active, not recruiting

Start Date: February 2014

Completed Date: July 2020

Phase: Phase 1/Phase 2

Type: Interventional


Primary Outcome: Maximum Tolerated Dose (MTD) Level for Drug Treatment Combination

Secondary Outcome: Response Rate

Study sponsors, principal investigator, and references

Principal Investigator: Charles Lu, MD

Lead Sponsor: Genprex, Inc.


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