Iloprost in Preventing Lung Cancer in Former Smokers

NCT02237183 | Completed Phase 1 DMC

• 7 other identifiers: NCI-2014-01891N01-CN-2012-00035HHSN2612201200035INCI2013-02-01NWU2013-02-01N01CN00035P30CA060553
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of iloprost compared with a placebo in preventing lung cancer in former smokers. Chemoprevention is the use of drugs to keep cancer from forming or coming back. Inhaled iloprost may help prevent lung cancer from forming in patients who used to smoke and who have been found to have abnormal cells in their mucus.

Conditions

Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of clinical toxicity

  Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Descriptive statistics (mean, standard deviation \[SD\], median, max, min and range) will be provided for toxicity. Approximate 95% confidence intervals will be used to assess the difference between treatment groups.

  Up to 90 days

• Treatment compliance, measured as the fraction of prescribed inhalations actually administered

  Descriptive statistics (mean, SD, median, max, min and range) will be provided for compliance. Approximate 95% confidence intervals will be used to assess the difference between treatment groups.

  Up to 60 days

Secondary Outcomes (6)

• Response of airway histology

  Up to 5 years

• Serum protein profiling

  Up to 60 days

• Endobronchial brushing gene expression

  Up to 60 days

• Gene expression of dysplastic lesions

  Up to 60 days

• Improvement in chronic obstructive pulmonary disease (COPD)

  Up to 60 days

Study Arms (4)

Arm I (iloprost QID)

EXPERIMENTAL

Patients receive iloprost via inhalation using a nebulizer QID for 60 days.

Drug: Iloprost; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm II (placebo QID)

PLACEBO COMPARATOR

Patients receive placebo via inhalation using a nebulizer QID for 60 days.

Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm III (iloprost BID)

EXPERIMENTAL

Patients receive iloprost via inhalation using a nebulizer BID for 60 days.

Drug: Iloprost; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm IV (placebo BID)

PLACEBO COMPARATOR

Patients receive placebo via inhalation using a nebulizer BID for 60 days.

Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Iloprost DRUG

Given via inhalation

Also known as: Ciloprost, Iloprost Clathrate, Ventavis, ZK 36374

Arm I (iloprost QID); Arm III (iloprost BID)

Placebo Administration OTHER

Given via inhalation

Arm II (placebo QID); Arm IV (placebo BID)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (iloprost QID); Arm II (placebo QID); Arm III (iloprost BID); Arm IV (placebo BID)

Questionnaire Administration OTHER

Ancillary studies

Arm I (iloprost QID); Arm II (placebo QID); Arm III (iloprost BID); Arm IV (placebo BID)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have either sputum cytologic atypia of mild dysplasia or greater or a history of bronchial biopsy with mild or greater dysplasia within the past 12 months
• Participants must have a smoking history of 20 pack-years or greater
• Participants must have the ability to safely undergo bronchoscopy in the judgment of the investigators
• Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Leukocytes \>= 3,000/microliter
• Platelets \>= 100,000/microliter
• Total bilirubin =\< 2.0 mg/dl
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 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 having intercourse with a woman of childbearing potential 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; Note: Women are considered to be of child-bearing potential if they are not surgically sterile or are under the age of 65 and have menstruated within the last two years
• Participants must be able to understand and willing to sign a written informed consent document

You may not qualify if:

• Participants must not have used any tobacco product in the past year
• Participants must not be currently receiving or have previously received thiazolidinedione treatment unless sputum atypia or endobronchial dysplasia are documented again after thiazolidinedione treatment and within 12 months of entry
• Participants must not have been treated with iloprost at any time; Note: participants on the placebo arm of previous iloprost trials are eligible, but participants on the placebo arm of cohort A of this study may not be enrolled in cohort B
• Participants must not have used any other investigation agent within the last six months
• Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition of iloprost
• Participants must not have 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 in the opinion of investigators would jeopardize patient safety of data integrity; Note: individuals who are human immunodeficiency virus (HIV) positive will not necessarily be excluded, will be considered on a case-by-case basis, but will be required to meet criteria related to patient safety and data integrity, as assessed by investigators
• Participants must not have a current or prior invasive malignancy within the past 6 months; participants may enroll prior to biopsy result report, unless there are findings at bronchoscopy suggesting an invasive malignancy; history of the following curatively treated cancers during any time prior to screening is allowed: non-melanoma skin cancer, cervical carcinoma in situ, and bladder carcinoma in situ
• Participants must not have received either chemotherapy or radiotherapy within the previous 6 months; Note: participants receiving long-term adjuvant hormonal therapy (such as tamoxifen or aromatase inhibitors for breast cancer) are allowed
• Women must not be pregnant or breastfeeding; iloprost is a prostacyclin agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iloprost, breastfeeding should be discontinued if the mother is treated with iloprost
• As iloprost inhibits platelet function, patients must not be taking anticoagulants, with the exception of aspirin or other non-steroidal anti-inflammatory medications
• Due to risk for hypotension in patients on vasodilators or antihypertensive medications, participants must not have blood pressure \< 95 mm Hg systolic

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Related Publications (1)

• Miller YE, Ghosh M, Merrick DT, Kubala B, Szabo E, Bengtson L, Kocherginsky M, Helenowski IB, Benante K, Schering T, Kim J, Kim H, Ha D, Bergan RC, Khan SA, Keith RL. Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment. Front Oncol. 2023 Aug 30;13:1204726. doi: 10.3389/fonc.2023.1204726. eCollection 2023.

  PMID: 37711198 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Iloprost

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• York E Miller

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 11, 2014
• Study Start: November 5, 2015
• Primary Completion: March 5, 2020
• Study Completion: August 30, 2023
• Last Updated: November 28, 2023

Record last verified: 2023-11

Locations

US (2)