Phase II Trial of Oral Iloprost for the Precision Chemoprevention of Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Change in numerical grade of the worst (highest grade on the WHO scale) dysplastic lesion per subject on bronchoscopy
研究概览
简要总结
This phase II trial tests whether oral iloprost works in preventing lung cancer (chemoprevention) in former smokers. Oral iloprost has previously been shown to reduce abnormal lung cells in former smokers, suggesting a clinically significant impact on lung cancer risk. The use of oral iloprost may help keep cancer from forming and reduce abnormal cells in the lung in order to lower the risk of developing lung cancer in former smokers.
详细描述
PRIMARY OBJECTIVE:
I.To determine if oral iloprost, starting at 50 ug twice daily (BID) and increased monthly to a final dose of 150 ug BID as tolerated, compared to placebo for 6 months is effective in reducing endobronchial dysplasia in former smokers who have mild or worse dysplasia on an endobronchial biopsy at baseline bronchoscopy.
SECONDARY OBJECTIVES:
I. To determine if treatment with oral iloprost compared to placebo results in a change in average dysplasia (over all sites of mild or greater dysplasia).
II. To determine safety of treatment with oral iloprost.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must be former smokers (> 12 months abstinent and confirmed by serum cotinine) with at least a 30 pack-year cigarette history who are at high risk for the development of lung cancer with at least one of the following:
- •Stage I or II lung cancer survivors, surgically treated with curative intent, who have remained disease free for > 12 months. Participants may have been treated with adjuvant chemotherapy or targeted therapy [(e.g. Osimertinib for epidermal growth factor receptor (EGFR) mutation)], if appropriate, provided they are > 12 months from the last systemic adjuvant therapy dose.
- •Patients with chronic obstructive pulmonary disease (COPD), defined as either airflow obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] < 0.70) on spirometry or emphysema (as commented on in a Radiology report) on CT scan.
- •Patients who display a ground glass opacity (GGO) on CT with a largest diameter =< 10 mm and >= 4 mm on axial imaging. The GGO must either be documented to have remained the same size or slowly progressing, but not regressing, over a 6-month period of observation by serial CT scan such that further workup beyond observation is not planned. A solid component of =< 1/3 of the axial diameter may be present, providing the treating physician(s) do not plan on workup for resection within the next 6 months, taking both the character of the lesion and its rate of growth into consideration.
- •Patients who have had a previous endobronchial biopsy with mild World Health Organization (WHO) score 4 or greater dysplasia
- •Participants must be able to safely undergo bronchoscopy in the judgement of the investigator
- •Participants must have a biopsy showing mild (grade 4 on WHO score) or greater dysplasia on the baseline bronchoscopy
- •Participants must be at least 50 years old. Because no dosing or adverse event (AE) data are currently available on the use of iloprost in participants <18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- •Leukocytes >= 3,000/microliter
- •Platelets >= 100,000/microliter
- •Total bilirubin =< 2.0 mg/dl
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 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 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.
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •The use of any tobacco product or inhalational nicotine delivery device in the past year
- •Taking any anticoagulant agent with the exception of aspirin
- •Taking any antiplatelet agent
- •Receiving any other investigational agents or the previous use of iloprost
- •Participants may not have received radiation therapy directed to the thorax or head and neck or immunotherapy, including checkpoint inhibitors
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to iloprost
- •A requirement of supplemental oxygen (O2) of >= 4 liter/minute to maintain an oxygen saturation of >= 90% at rest
- •A biopsy on baseline bronchoscopy with a dysplasia score of 7 or 8 (carcinoma in situ or invasive cancer)
- •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 would limit compliance with study requirements.
- •Pregnant women are excluded from this study because iloprost is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with iloprost breastfeeding should be discontinued if the mother is treated with iloprost.
- •Due to the risk for hypotension due to vasodilator effect of iloprost, participants must not have a blood pressure < 95 mm Hg systolic
- •Participants must not have a current or prior invasive cancer within the past 12 months. History of the following cancers, curatively treated by surgery or locally ablative means, at any time prior to screening is allowed: non-melanoma skin cancer and cervical carcinoma in situ. Participants with prostate cancer undergoing active surveillance are allowed.
- •Participants being treated with hormonal or immune therapies, including intravesicular bacillus calmette-guerin (BCG), are excluded
- •Survivors of curatively treated stage III non-small cell lung cancer (NSCLC) or any stage lung small cell carcinoma (SCLC) are excluded
- •Patients with known metastatic cancer of any kind are excluded
- •Participants with known underlying bleeding disorders are excluded
研究组 & 干预措施
Arm I (iloprost)
Patients receive Iloprost PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Biospecimen Collection (Procedure)
Arm I (iloprost)
Patients receive Iloprost PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Bronchial Brush Biopsy (Procedure)
Arm I (iloprost)
Patients receive Iloprost PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Bronchoscopy (Procedure)
Arm I (iloprost)
Patients receive Iloprost PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Iloprost (Drug)
Arm I (iloprost)
Patients receive Iloprost PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Questionnaire Administration (Other)
Arm II (placebo)
Patients receive placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Biospecimen Collection (Procedure)
Arm II (placebo)
Patients receive placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Bronchial Brush Biopsy (Procedure)
Arm II (placebo)
Patients receive placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Bronchoscopy (Procedure)
Arm II (placebo)
Patients receive placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Placebo Administration (Drug)
Arm II (placebo)
Patients receive placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Change in numerical grade of the worst (highest grade on the WHO scale) dysplastic lesion per subject on bronchoscopy
时间窗: Baseline to 6 month follow up
Histologic response is the mean change between baseline and 6 month follow up bronchoscopy in the numerical grade of the worst (highest grade on the World Health Organization \[WHO\] scale) dysplastic lesion per subject. Will be analyzed using a linear regression models with post-treatment worst grade dysplasia as the outcome variable, and treatment arm (iloprost and placebo) and baseline worst grade dysplasia as predictors.
次要结局
- Incidence of adverse events with oral iloprost(From first dose to end of study, assessed up to 6 months)
- Change in the average WHO score of all biopsy sites with a baseline score of 4 or greater(Up to 6 months)