Completed

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

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What is being tested

iloprost

+ placebo
Drug
Other
Who is being recruted

Lung Cancer

+ Precancerous Condition
From 18 to 85 Years

See all eligibility criteria

How is the trial designed

Prevention Study

Placebo-Controlled
Phase 2
Interventional
Study Start: November 2001

See protocol details

Summary

Principal SponsorUniversity of Colorado, Denver
Last updated: May 14, 2020
Sourced from a government-validated database.Claim as a partner
Study start date: November 1, 2001Actual date on which the first participant was enrolled.

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. 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. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to smoking status (current vs former) and participating center. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral iloprost twice daily. * Arm II: Patients receive oral placebo twice daily. In both arms, treatment continues for 6 months in the absence of unacceptable toxicity. Patients are followed at 1 month and then annually thereafter. PROJECTED ACCRUAL: A total of 152 patients (76 \[38 current smokers and 38 former smokers\] per treatment arm) will be accrued for this study within 2 years.

Official TitleA Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer 
Principal SponsorUniversity of Colorado, Denver
Last updated: May 14, 2020
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
152 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Prevention Study
Prevention studies aim to stop a disease from developing. They often involve people at risk and test things like vaccines, lifestyle changes, or preventive medications.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a placebo-controlled study, some participants receive the experimental treatment, while others receive an inert substance (placebo) to compare outcomes. This method helps to isolate the effect of the treatment from the psychological effects of receiving any treatment at all.

Other Options
Non-placebo-controlled: No placebo is used. All participants receive the actual treatment or alternative interventions (often the Standard of Care), and comparisons are made between these treatments.

How the interventions assigned to participants is kept confidential
Participants, researchers, and outcome assessors do not know which treatment is being given. This helps reduce bias not just during the study, but also when the results are being evaluated.

Other Ways to Mask Information
Open-label: Everyone knows which treatment is being given.
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 18 to 85 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Lung Cancer
Precancerous Condition
Criteria

Inclusion Criteria: * 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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

50% chance 

of being blinded to the placebo group

Treatment Groups
Group I
Experimental
Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.
Group II
Placebo
Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.
Study Objectives
Primary Objectives

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.
Secondary Objectives

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 6 locations
Suspended
University of Colorado Cancer Center at UC Health Sciences CenterAurora, United StatesSee the location
Suspended
Veterans Affairs Medical Center - DenverDenver, United States
Suspended
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, United States
Suspended
Mayo Clinic Cancer CenterRochester, United States
Completed6 Study Centers