Phase I/II Clinical Trial Combining TUSC2-nanoparticles and Erlotinib in Stage IV Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) Level for Drug Treatment Combination
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically documented non-small cell lung cancer (NSCLC)
- •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.
- •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)
- •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.
- •ECOG or Zubrod Performance Status ≤1
- •Age ≥18 years
- •Subjects must have voluntarily signed an informed consent in accordance with institutional policies.
- •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.
- •Subjects are required to agree to practice effective birth control (i.e., abstinence, intrauterine device for female subjects) during the study period.
- •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.
- •ANC >1500/mm3, platelet count >100,000/mm3 ≤14 days of study treatment
- •PT and PTT <1.25 times the institutional upper limit of normal ≤14 days of study treatment
- •Adequate renal function documented by serum creatinine of ≤1.5 mg/dl or calculated creatinine clearance >50 ml/min ≤14 days of study treatment
- •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
- •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.
- •Stable cardiac condition with a left ventricular ejection fraction ≥40% ≤28 days of study treatment
排除标准
- •Subject is female who is pregnant or breast-feeding.
- •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.
- •Subject received standard chemotherapy with FDA-approved agents within ≤21 days of start of study treatment.
- •Subject received a targeted therapy within ≤14 days prior to start of study treatment.
- •Subject has active systemic viral, bacterial or fungal infection(s) requiring treatment.
- •Subject has brain metastases (except as allowed in Section 3.2.1). Neurological assessment will be used to determine brain metastases.
- •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.
- •Subject received prior gene therapy or cell therapy.
- •Subject has history of myocardial infarction or unstable angina ≤6 months of start of study treatment.
- •Subject is known to be HIV positive.
研究组 & 干预措施
DOTAP + Erlotinib
DOTAP: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.
干预措施: Erlotinib (Drug)
DOTAP + Erlotinib
DOTAP: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.
干预措施: Dexamethasone (Drug)
DOTAP + Erlotinib
DOTAP: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.
干预措施: Diphenhydramine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) Level for Drug Treatment Combination
时间窗: First 21 day cycle
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).
次要结局
- Response Rate(After two, 21 day cycles)