Bronchial Epithelial DysplasiaPhase 2NCT05411107
Oral Iloprost for the Prevention of Lung Cancer In Former Smokers
A Phase 2 study testing Biospecimen Collection, Bronchial Brush Biopsy and Bronchoscopy in people with Bronchial Epithelial Dysplasia and Chronic Obstructive Pulmonary Disease, run by National Cancer Institute (NCI).
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Bronchial Epithelial Dysplasia, Chronic Obstructive Pulmonary Disease, Lung Carcinoma
- What is being tested?
- Biospecimen Collection, Bronchial Brush Biopsy and Bronchoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2024to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
About this study
Official title: Phase II Trial of Oral Iloprost for the Precision Chemoprevention of Lung Cancer
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.
Read the detailed description
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:
- 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.
EXPLORATORY OBJECTIVES:
- To determine if treatment with oral iloprost compared to placebo results in a change in response rate defined as >= 1 point reduction in maximum dysplasia.
II. To determine if the in vitro differentiation response of bronchial epithelial cell progenitors cultured at the air liquid interface is predictive of the in vivo response of dysplasia improvement (to be done only in participants recruited in Colorado).
III. To determine if treatment with oral iloprost compared to placebo results in a decrease in the volume of pure ground glass opacities (GGOs) on chest computed tomography (CT).
IV. To determine if treatment with oral iloprost compared to placebo increases peripheral lung epithelial progenitor counts, measured by organoid formation in a three dimensional culture system seeded from distal airway brushings (to be done only in participants recruited in Colorado).
- To determine if oral iloprost reduces the incidence of lung cancer compared to placebo.
VI. To evaluate the ability of 3-dimensional morphologic analysis of expectorated sputum by LuCED compared to standard sputum cytopathology to predict endobronchial dysplasia and measure response to iloprost.
VII. To evaluate histologic response by alternative criteria.
OUTLINE: Patients are randomized in 1 of 2 arms.
ARM I: Patients receive iloprost orally (PO) BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
ARM II: Patients receive iloprost placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Bronchial Epithelial Dysplasia, Chronic Obstructive Pulmonary Disease, Lung Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Tobacco-Related Carcinoma
- Being tested
- Biospecimen Collection, Bronchial Brush Biopsy, Bronchoscopy, Iloprost, Placebo Administration
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of sputum sample
Bronchial Brush BiopsyProcedure or surgery
Also called bronchial brushing
Undergo bronchial brush biopsy
BronchoscopyProcedure or surgery
Undergo bronchoscopy
IloprostDrug
Also called Ciloprost, Iloprost Clathrate, Ventavis, ZK 36374
Given PO
Placebo AdministrationDrug
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (iloprost) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bronchial Brush Biopsy; Procedure: Bronchoscopy; Drug: Iloprost; Other: Questionnaire Administration |
| Arm II (placebo) | Placebo comparator | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bronchial Brush Biopsy; Procedure: Bronchoscopy; Drug: Placebo Administration; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in numerical grade of the worst (highest grade on the WHO scale) dysplastic lesion per subject on bronchoscopy
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.
Measured: Baseline to 6 month follow up
Secondary outcomes (2)
Change in the average WHO score of all biopsy sites with a baseline score of 4 or greater
Will be assessed using bronchial biopsies according to the WHO grading system, where 1 is normal and 8 is invasive cancer.
Measured: Up to 6 months
Incidence of adverse events with oral iloprost
Safety will be assessed according to a comparison of adverse events (AEs) between iloprost and placebo participants. Descriptive statistics (frequency, percent) will be used to summarize participants' worst grade toxicity for each AE type. AE rates will be compared between treatment arms using Fisher's exact test since AE rates are expected to be low.
Measured: From first dose to end of study, assessed up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2022
- Study start1 Jun 2024 (estimated)
- Primary completion1 Dec 2026 (estimated)
- Study completion30 Jun 2027 (estimated)
Why it stopped: Agent is not available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bronchial Epithelial DysplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- York E Miller, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05411107
- Sponsor's protocol ID
- NCI-2022-04698
- Other IDs
- NCI-2022-04698, NCI21-08-01, NWU21-08-01, P30CA060553, UG1CA242643
- Status last verified
- May 2024
- First submitted
- 8 Jun 2022
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Oral Iloprost for the Precision Chemoprevention of Lung Cancer
- ClinicalTrials.gov ID
- NCT05411107
- Acronym / sponsor ID
- NCI-2022-04698
- Conditions
- Bronchial Epithelial Dysplasia, Chronic Obstructive Pulmonary Disease, Lung Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Tobacco-Related Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Agent is not available
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 9 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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.
EXPLORATORY OBJECTIVES:
- To determine if treatment with oral iloprost compared to placebo results in a change in response rate defined as >= 1 point reduction in maximum dysplasia.
II. To determine if the in vitro differentiation response of bronchial epithelial cell progenitors cultured at the air liquid interface is predictive of the in vivo response of dysplasia improvement (to be done only in participants recruited in Colorado).
III. To determine if treatment with oral iloprost compared to placebo results in a decrease in the volume of pure ground glass opacities (GGOs) on chest computed tomography (CT).
IV. To determine if treatment with oral iloprost compared to placebo increases peripheral lung epithelial progenitor counts, measured by organoid formation in a three dimensional culture system seeded from distal airway brushings (to be done only in participants recruited in Colorado).
- To determine if oral iloprost reduces the incidence of lung cancer compared to placebo.
VI. To evaluate the ability of 3-dimensional morphologic analysis of expectorated sputum by LuCED compared to standard sputum cytopathology to predict endobronchial dysplasia and measure response to iloprost.
VII. To evaluate histologic response by alternative criteria.
OUTLINE: Patients are randomized in 1 of 2 arms.
ARM I: Patients receive iloprost orally (PO) BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
ARM II: Patients receive iloprost placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (iloprost) | Experimental | Procedure: Biospecimen Collection, Procedure: Bronchial Brush Biopsy, Procedure: Bronchoscopy, Drug: Iloprost, Other: Questionnaire AdministrationPatients receive Iloprost PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180. |
| Arm II (placebo) | Placebo comparator | Procedure: Biospecimen Collection, Procedure: Bronchial Brush Biopsy, Procedure: Bronchoscopy, Drug: Placebo Administration, Other: Questionnaire AdministrationPatients receive placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- 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%)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo collection of sputum sample | Procedure or surgery | Arm I (iloprost), Arm II (placebo) |
| Bronchial Brush BiopsyAlso: bronchial brushingUndergo bronchial brush biopsy | Procedure or surgery | Arm I (iloprost), Arm II (placebo) |
| BronchoscopyUndergo bronchoscopy | Procedure or surgery | Arm I (iloprost), Arm II (placebo) |
| IloprostAlso: Ciloprost, Iloprost Clathrate, Ventavis, ZK 36374Given PO | Drug | Arm I (iloprost) |
| Placebo AdministrationGiven PO | Drug | Arm II (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Arm I (iloprost), Arm II (placebo) |
Primary outcome
Change in numerical grade of the worst (highest grade on the WHO scale) dysplastic lesion per subject on bronchoscopy
Time frame: 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.
2 secondary outcomes
Change in the average WHO score of all biopsy sites with a baseline score of 4 or greater
Time frame: Up to 6 months
Incidence of adverse events with oral iloprost
Time frame: From first dose to end of study, assessed up to 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
York E Miller principal investigator
Northwestern University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biospecimen Collection, Bronchial Brush Biopsy and Bronchoscopy in people with Bronchial Epithelial Dysplasia and Chronic Obstructive Pulmonary Disease, run by National Cancer Institute (NCI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in numerical grade of the worst (highest grade on the WHO scale) dysplastic lesion per subject on bronchoscopy (time frame: Baseline to 6 month follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.