Lung Cancer | FUS1-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-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.
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 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.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
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-fus1Starting 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-fus1 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 FUS1
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-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.
Start Date: February 2014
Phase: Phase 1/Phase 2
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.