Trial Outcomes & Findings for Iloprost in Preventing Lung Cancer in Patients at High Risk for This Disease (NCT NCT00084409)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

152 participants

Primary outcome timeframe

Nine years

Results posted on

2020-05-14

Participant Flow

The majority of patients were recruited between November 2002 and July 2008 from from pulmonary medicine clinics.

Patients were excluded from randomization according to the exclusion criteria which included prior history of cancer, significant comorbid disease or inability to undergo 2 bronchoscopies, hypoxemia with the required use of supplemental oxygen, use of inhaled steroids within 6 weeks of enrollment, and carcinoma in situ or invasive cancer on bronch.

Participant milestones

Participant milestones
Measure	Iloprost Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.	Placebo Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.
Overall Study STARTED	75	77
Overall Study COMPLETED	60	65
Overall Study NOT COMPLETED	15	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Iloprost in Preventing Lung Cancer in Patients at High Risk for This Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Iloprost n=75 Participants Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.	Placebo n=77 Participants Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.	Total n=152 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=5 Participants	62 Participants n=7 Participants	119 Participants n=5 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Age, Continuous	58 years STANDARD_DEVIATION 11 • n=5 Participants	58 years STANDARD_DEVIATION 9 • n=7 Participants	58 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	19 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	58 Participants n=7 Participants	110 Participants n=5 Participants
Region of Enrollment United States	75 participants n=5 Participants	77 participants n=7 Participants	152 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Average (Follow-up - Baseline) From All Biopsies	-0.23 WHO Units Standard Deviation 0.77	-0.02 WHO Units Standard Deviation 0.79

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: From all biopsies scored at the baseline bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated (this is the definition of Dysplasia Index (DI)). From all biopsies scored at the follow-up bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated. The difference (follow-up DI - baseline DI) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Dysplasia Index (Follow-up - Baseline) Using All Biopsies	-7.70 Percentage points Standard Deviation 21.76	-0.92 Percentage points Standard Deviation 25.23

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: The biopsies used in this analysis are those from the following 6 anatomical sites pre-specified in the protocol to be biopsied: RUL (Right upper lobe: the superior region of the right lung), RML (Right middle lobe: an anatomic portion of the right lung), RB6 (The carina in the right lower lobe at the entrance to the superior segment), LUL (Left upper lobe: the superior portion of the lung), LUDB (Left upper division bronchus: the carina between the lingular orifice and the left upper lobe), and LB6 (The carina in the left lower lobe at the entrance to the superior segment). From these biopsies scored at the baseline bronchoscopy, the mean WHO score is calculated. From these biopsies scored at the follow-up bronchoscopy, the mean WHO score is calculated. The difference (follow-up mean - baseline mean) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Average (Follow-up - Baseline) Using Reference Sites	-0.23 WHO Units Standard Deviation 0.82	-0.01 WHO Units Standard Deviation 0.82

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: The biopsies used in this analysis are those from the following 6 anatomical sites pre-specified in the protocol to be biopsied: RUL, RML, RB6, LUL, LUDB, and LB6. From these biopsies scored at the baseline bronchoscopy, the maximum WHO score is used. From these biopsies scored at the follow-up bronchoscopy, the maximum WHO score is used. The difference (follow-up maximum - baseline maximum) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Maximum (Follow-up - Baseline) Using Reference Sites	-0.35 WHO Units Standard Deviation 1.58	0.11 WHO Units Standard Deviation 1.30

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: The biopsies used in this analysis are those from the following 6 anatomical sites pre-specified in the protocol to be biopsied: RUL, RML, RB6, LUL, LUDB, and LB6. From these biopsies scored at the baseline bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated (this is the definition of Dysplasia Index (DI)). From these biopsies scored at the follow-up bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated. The difference (follow-up DI - baseline DI) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Dysplasia Index (Follow-up - Baseline) Using Reference Sites	-7.61 Percentage points Standard Deviation 23.43	0.15 Percentage points Standard Deviation 26.41

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: The biopsies used in this analysis are restricted to biopsies from anatomical sites that were biopsies during both the baseline and follow-up bronchoscopies, thus creating "pairs" of biopsies. From these biopsies scored at the baseline bronchoscopy, the mean WHO score is calculated. From these biopsies scored at the follow-up bronchoscopy, the mean WHO score is calculated. The difference (follow-up mean - baseline mean) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Average (Follow-up - Baseline) Using Matched Sites	-0.24 WHO Units Standard Deviation 0.78	-0.06 WHO Units Standard Deviation 0.86

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: The biopsies used in this analysis are restricted to biopsies from anatomical sites that were biopsies during both the baseline and follow-up bronchoscopies. From these biopsies scored at the baseline bronchoscopy, the maximum WHO score is used. From these biopsies scored at the follow-up bronchoscopy, the maximum WHO score is used. The difference (follow-up maximum - baseline maximum) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Maximum (Follow-up - Baseline) Using Matched Sites	-0.53 WHO Units Standard Deviation 1.46	0.11 WHO Units Standard Deviation 1.26

SECONDARY outcome

Timeframe: 9 Years

This outcome measure is created for each subject as follows: The biopsies used in this analysis are restricted to biopsies from anatomical sites that were biopsies during both the baseline and follow-up bronchoscopies. From these biopsies scored at the baseline bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated (this is the definition of Dysplasia Index (DI)). From these biopsies scored at the follow-up bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated. The difference (follow-up DI - baseline DI) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=60 Participants	Placebo n=65 Participants
Change in Dysplasia Index (Follow-up - Baseline) Using Matched Sites	-7.97 Percentage points Standard Deviation 22.13	-2.34 Percentage points Standard Deviation 25.49

SECONDARY outcome

Timeframe: 9 Years

Population: The analysis was restricted to the 107 subjects (52 in the iloprost group, 55 in the placebo group) with at least 1 non-normal biopsy at baseline, thereby excluding the 18 subjects (8 in the iloprost group and 10 in the placebo group) who had only normal biopsy tissue at baseline.

This outcome measure is created for each subject as follows: The biopsies used in this analysis are restricted to biopsies from anatomical sites that were biopsies during both the baseline and follow-up bronchoscopies, thus creating "pairs" of biopsies. Any "pair" for which the baseline WHO score was 1 (i.e. normal tissue) was excluded from the analysis. From these biopsies scored at the baseline bronchoscopy, the mean WHO score is calculated. From these biopsies scored at the follow-up bronchoscopy, the mean WHO score is calculated. The difference (follow-up mean - baseline mean) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=52 Participants	Placebo n=55 Participants
Change in Average (Follow-up - Baseline) Using Baseline Non-Normal Pairs	-0.71 WHO Units Standard Deviation 0.93	-0.38 WHO Units Standard Deviation 0.99

SECONDARY outcome

Timeframe: 9 Years

Population: The analysis was restricted to the 107 subjects (52 in the iloprost group, 55 in the placebo group) with at least 1 non-normal biopsy at baseline, thereby excluding the 18 subjects (8 in the iloprost group and 10 in the placebo group) who had only normal biopsy tissue at baseline.

This outcome measure is created for each subject as follows: The biopsies used in this analysis are restricted to biopsies from anatomical sites that were biopsies during both the baseline and follow-up bronchoscopies, thus creating "pairs" of biopsies. Any "pair" for which the baseline WHO score was 1 (i.e. normal tissue) was excluded from the analysis. From these biopsies scored at the baseline bronchoscopy, the maximum WHO score is used. From these biopsies scored at the follow-up bronchoscopy, the maximum WHO score is used. The difference (follow-up maximum - baseline maximum) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=52 Participants	Placebo n=55 Participants
Change in Maximum (Follow-up - Baseline) Using Baseline Non-Normal Pairs	-0.81 WHO Units Standard Deviation 1.46	-0.13 WHO Units Standard Deviation 1.26

SECONDARY outcome

Timeframe: 9 Years

Population: The analysis was restricted to the 107 subjects (52 in the iloprost group, 55 in the placebo group) with at least 1 non-normal biopsy at baseline, thereby excluding the 18 subjects (8 in the iloprost group and 10 in the placebo group) who had only normal biopsy tissue at baseline.

This outcome measure is created for each subject as follows: The biopsies used in this analysis are restricted to biopsies from anatomical sites that were biopsies during both the baseline and follow-up bronchoscopies, thus creating "pairs" of biopsies. Any "pair" for which the baseline WHO score was 1 (i.e. normal tissue) was excluded from the analysis. From these biopsies scored at the baseline bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated (this is the definition of Dysplasia Index (DI)). From these biopsies scored at the follow-up bronchoscopy, the percentage with a WHO score greater than or equal to 4 is calculated. The difference (follow-up DI - baseline DI) is used as the outcome measure for each subject.

Outcome measures

Outcome measures
Measure	Iloprost n=52 Participants	Placebo n=55 Participants
Change in Dysplasia Index (Follow-up - Baseline) Using Baseline Non-Normal Pairs	-14.32 Percentage points Standard Deviation 31.39	-6.48 Percentage points Standard Deviation 34.26

OTHER_PRE_SPECIFIED outcome

Timeframe: nine years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Nine years

PGIS (Prostacyclin synthase: an enzyme in the eicosanoid pathway that catalyzes the conversion of prostaglandin H2 to prostaglandin I2 (prostacyclin). PPAR (Peroxisome proliferator-activated receptor: a group of nuclear receptor proteins that act as transcription factors regulating gene expression),

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Nine Years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Nine Years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 9 years

To determine if Iloprost can modulate a panel of biomarkers including MCM-2, EGFR, Her-2/neu, RARβ, p53, FHIT, apoptotic index, and microvessel density.

Outcome measures

Outcome data not reported

Adverse Events

Iloprost

Serious events: 3 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Iloprost n=75 participants at risk Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.	Placebo n=77 participants at risk Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.
General disorders Hospitalization	4.0% 3/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	5.2% 4/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
General disorders Death	0.00% 0/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	1.3% 1/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
Nervous system disorders CVA - Stroke	0.00% 0/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	1.3% 1/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database

Other adverse events

Other adverse events
Measure	Iloprost n=75 participants at risk Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.	Placebo n=77 participants at risk Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.This group consisted of current and former smokers.
Nervous system disorders Headache	53.3% 40/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	22.1% 17/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
Vascular disorders Flushing	24.0% 18/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	7.8% 6/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
Gastrointestinal disorders Nausea	16.0% 12/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	7.8% 6/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
General disorders Pain - Other	16.0% 12/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	7.8% 6/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
Musculoskeletal and connective tissue disorders Myalgia (muscle pain)	17.3% 13/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	1.3% 1/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
General disorders Fatigue	10.7% 8/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	2.6% 2/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
Investigations Metabolic/Laboratory - Other	4.0% 3/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	7.8% 6/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database
Nervous system disorders Neuropathic pain	9.3% 7/75 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database	1.3% 1/77 • 6 Years Adverse event collection was obtained at monthly visits on all randomized participants according to the NCI CommonToxicity criteria version 2.0, entered in case report forms, and in the NCI Oracle Clinical Database

Additional Information

Robert Keith, M.D.

University of Colorado Denver

Phone: 303-399-8020

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place