A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 152
- 试验地点
- 6
- 主要终点
- Change in Average (Follow-up - Baseline) From All Biopsies
研究概览
简要总结
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Iloprost may be effective in preventing lung cancer.
PURPOSE: This randomized phase II trial is studying how well iloprost works in preventing lung cancer in patients who are at high risk for this disease.
详细描述
OBJECTIVES:
Primary
- Compare the reversal of premalignant histological changes in the bronchial epithelium of patients at high risk for lung cancer (defined by > 20 pack years of smoking and sputum atypia) treated with iloprost vs placebo.
- Determine whether this drug modulates Ki-67 proliferation index (Antigen Ki-67) in these patients.
- Determine whether this drug affects prostaglandin metabolism in these patients.
- Determine the toxicity profile of this drug in these patients.
Secondary
- Determine whether this drug modulates a panel of biomarkers, including MCM-2(Minichromosome maintenance protein: forms DNA helicase), EGFR (Epidermal growth factor receptor: cell surface receptor for the epidermal growth factor family of proteins. Mutations in EGFR expression or activity can result in cancer.) , HER2/neu (Human epidermal growth factor receptor 2 HER2 is a member of the EGFR family), RARβ (Retinoic Acic Receptor Beta is a nuclear transcription regulator and a member of the thyroid-steroid hormone receptor superfamily), p53, FHIT (Fragile histidine triad protein is an enzyme involved in purine metabolism and had been demonstrated to be a tumor suppressor), apoptotic index, and microvessel density, in these patients.
- Determine the genes whose expression is altered by this drug in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, 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
- •Current or former smoker with ≥ 20 pack-year history of smoking with no tobacco use within the past 6 months
- •Mild atypia or worse on sputum cytology, or
- •Bronchial biopsy with mild or worse dysplasia within the past 12 months
- •Age 18 and over
- •SWOG (Southwest Oncology Group)0-2
- •Life expectancy at least 6 months
- •Granulocyte count > 1,500/mm^3
- •Platelet count > 100,000/mm^3
- •Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
- •Transaminases ≤ 2.5 times ULN
- •Bilirubin ≤ 2.0 mg/dL
- •Albumin ≥ 2.5 g/dL
- •Creatinine ≤ 1.5 mg/dL
- •Well-controlled atrial fibrillation OR rare (< 2 minutes) premature ventricular contractions allowed
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able and willing to undergo bronchoscopy
- •Exclusion Criteria
- •Clinically apparent bleeding diathesis
- •Ventricular tachycardia
- •Multifocal premature ventricular contractions or supraventricular tachycardias with rapid ventricular response
- •Pneumonia or acute bronchitis within the past 2 weeks
- •Hypoxemia (< 90% saturation with supplemental oxygen)
- •Pregnant or nursing
- •Malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •Serious medical condition that would preclude bronchoscopy or study participation
- •Clinically active coronary artery disease
- •Myocardial infarction within the past 6 weeks
- •Chest pain
- •Congestive heart failure
- •Cardiac dysrhythmia that is potentially life-threatening
- •Exclusion for PRIOR CONCURRENT THERAPY:
- •Biologic therapy (Not specified)
- •More than 5 years since prior chemotherapy
- •More than 6 weeks since prior inhaled steroids
- •More than 5 years since prior thoracic radiotherapy
- •Surgery (Not specified)
- •No prior prostacyclin
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.
干预措施: iloprost (Drug)
Arm II
Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.
干预措施: placebo (Other)
结局指标
主要结局
Change in Average (Follow-up - Baseline) From All Biopsies
时间窗: Nine years
This outcome measure is created for each subject as follows: From all biopsies scored at the baseline bronchoscopy, the mean WHO score is calculated. From all biopsies scored at the follow-up bronchoscopy, the mean WHO score is calculated.Histology on bronchial biopsies pre-treatment and post-treatment will be compared. All biopsies will be graded according to the WHO classification for bronchial epithelium for this outcome, and all the following outcomes. WHO Classification Grade Normal 1.0 Reserve Cell Hyperplasia 2.0 Metaplasia 3.0 Mild Dysplasia 4.0 Moderate Dysplasia 5.0 Severe Dysplasia 6.0 Carcinoma in Situ 7.0 Carcinoma 8.0 The difference (follow-up mean - baseline mean) is used as the outcome measure for each subject.
次要结局
- Change in Maximum (Follow-up - Baseline) Using Reference Sites(9 Years)
- Change in Average (Follow-up - Baseline) Using Matched Sites(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using Matched Sites(9 Years)
- Change in Maximum (Follow-up - Baseline) Using Matched Sites(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using All Biopsies(9 Years)
- Change in Average (Follow-up - Baseline) Using Reference Sites(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using Reference Sites(9 Years)
- Change in Maximum (Follow-up - Baseline) Using Baseline Non-Normal Pairs(9 Years)
- Change in Average (Follow-up - Baseline) Using Baseline Non-Normal Pairs(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using Baseline Non-Normal Pairs(9 Years)