A Phase I Trial of Inhaled Iloprost for the Prevention of Lung Cancer in Former Smokers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Incidence of clinical toxicity
研究概览
简要总结
This phase I trial studies the side effects and best dose of iloprost compared with a placebo in preventing lung cancer in former smokers. Chemoprevention is the use of drugs to keep cancer from forming or coming back. Inhaled iloprost may help prevent lung cancer from forming in patients who used to smoke and who have been found to have abnormal cells in their mucus.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the toxicity of inhalational iloprost administered to patients daily for 2 months, given four times a day (QID).
SECONDARY OBJECTIVES:
I. To evaluate the compliance QID dosing regimens. II. To evaluate the effect on endobronchial histology. III. To evaluate the effect on expectorated sputum cytology by both standard cytologic analysis and an automated three-dimensional morphologic analysis.
IV. To evaluate the effect on endobronchial brushing and biopsy gene expression of peroxisome proliferator-activated receptor gamma (PPARgamma), glutathione S-transferase mu (GSTmu), carboxylesterase 1 (Ces1), Fos-related antigen 1 (FosL1), cytochrome p4502e1, stearoyl coA desaturase 1, tumor necrosis factor (TNF) superfamily member 9, transforming growth factor beta (TGFbeta), Jun and a 46 gene panel associated with dysplasia persistence, using Affymetrix arrays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have either sputum cytologic atypia of mild dysplasia or greater or a history of bronchial biopsy with mild or greater dysplasia within the past 12 months
- •Participants must have a smoking history of 20 pack-years or greater
- •Participants must have the ability to safely undergo bronchoscopy in the judgment of the investigators
- •Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Leukocytes >= 3,000/microliter
- •Platelets >= 100,000/microliter
- •Total bilirubin =< 2.0 mg/dl
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
- •Creatinine =< 2.0 mg/dl
- •The effects of iloprost on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because prostacyclins are known to be teratogenic, women of child-bearing potential and men having intercourse with a woman of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; Note: Women are considered to be of child-bearing potential if they are not surgically sterile or are under the age of 65 and have menstruated within the last two years
- •Participants must be able to understand and willing to sign a written informed consent document
排除标准
- •Participants must not have used any tobacco product in the past year
- •Participants must not be currently receiving or have previously received thiazolidinedione treatment unless sputum atypia or endobronchial dysplasia are documented again after thiazolidinedione treatment and within 12 months of entry
- •Participants must not have been treated with iloprost at any time; Note: participants on the placebo arm of previous iloprost trials are eligible, but participants on the placebo arm of cohort A of this study may not be enrolled in cohort B
- •Participants must not have used any other investigation agent within the last six months
- •Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition of iloprost
- •Participants must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that in the opinion of investigators would jeopardize patient safety of data integrity; Note: individuals who are human immunodeficiency virus (HIV) positive will not necessarily be excluded, will be considered on a case-by-case basis, but will be required to meet criteria related to patient safety and data integrity, as assessed by investigators
- •Participants must not have a current or prior invasive malignancy within the past 6 months; participants may enroll prior to biopsy result report, unless there are findings at bronchoscopy suggesting an invasive malignancy; history of the following curatively treated cancers during any time prior to screening is allowed: non-melanoma skin cancer, cervical carcinoma in situ, and bladder carcinoma in situ
- •Participants must not have received either chemotherapy or radiotherapy within the previous 6 months; Note: participants receiving long-term adjuvant hormonal therapy (such as tamoxifen or aromatase inhibitors for breast cancer) are allowed
- •Women must not be pregnant or breastfeeding; iloprost is a prostacyclin agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iloprost, breastfeeding should be discontinued if the mother is treated with iloprost
- •As iloprost inhibits platelet function, patients must not be taking anticoagulants, with the exception of aspirin or other non-steroidal anti-inflammatory medications
- •Due to risk for hypotension in patients on vasodilators or antihypertensive medications, participants must not have blood pressure < 95 mm Hg systolic
研究组 & 干预措施
Arm I (iloprost QID)
Patients receive iloprost via inhalation using a nebulizer QID for 60 days.
干预措施: Quality-of-Life Assessment (Other)
Arm I (iloprost QID)
Patients receive iloprost via inhalation using a nebulizer QID for 60 days.
干预措施: Questionnaire Administration (Other)
Arm I (iloprost QID)
Patients receive iloprost via inhalation using a nebulizer QID for 60 days.
干预措施: Iloprost (Drug)
Arm II (placebo QID)
Patients receive placebo via inhalation using a nebulizer QID for 60 days.
干预措施: Placebo Administration (Other)
Arm II (placebo QID)
Patients receive placebo via inhalation using a nebulizer QID for 60 days.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo QID)
Patients receive placebo via inhalation using a nebulizer QID for 60 days.
干预措施: Questionnaire Administration (Other)
Arm III (iloprost BID)
Patients receive iloprost via inhalation using a nebulizer BID for 60 days.
干预措施: Iloprost (Drug)
Arm III (iloprost BID)
Patients receive iloprost via inhalation using a nebulizer BID for 60 days.
干预措施: Quality-of-Life Assessment (Other)
Arm III (iloprost BID)
Patients receive iloprost via inhalation using a nebulizer BID for 60 days.
干预措施: Questionnaire Administration (Other)
Arm IV (placebo BID)
Patients receive placebo via inhalation using a nebulizer BID for 60 days.
干预措施: Placebo Administration (Other)
Arm IV (placebo BID)
Patients receive placebo via inhalation using a nebulizer BID for 60 days.
干预措施: Quality-of-Life Assessment (Other)
Arm IV (placebo BID)
Patients receive placebo via inhalation using a nebulizer BID for 60 days.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Incidence of clinical toxicity
时间窗: Up to 90 days
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Descriptive statistics (mean, standard deviation \[SD\], median, max, min and range) will be provided for toxicity. Approximate 95% confidence intervals will be used to assess the difference between treatment groups.
Treatment compliance, measured as the fraction of prescribed inhalations actually administered
时间窗: Up to 60 days
Descriptive statistics (mean, SD, median, max, min and range) will be provided for compliance. Approximate 95% confidence intervals will be used to assess the difference between treatment groups.
次要结局
- Response of airway histology(Up to 5 years)
- Endobronchial brushing gene expression(Up to 60 days)
- Improvement in chronic obstructive pulmonary disease (COPD)(Up to 60 days)
- Whether the in vitro response of cultured airway epithelial progenitor cells to iloprost is a predictor of in vivo response in study subjects(Up to 60 days)
- Gene expression of dysplastic lesions(Up to 60 days)
- Serum protein profiling(Up to 60 days)