Lung Cancer
Conditions
Keywords
Healthy, Prevention
Brief summary
To compare the difference of a marker of cellular proliferation in all bronchial biopsy specimens of former smokers stratified by lung cancer risk, collected before and after treatment per patient between the enzastaurin and placebo groups.
Interventions
DRUGEnzastaurin
500 mg po QD for 6 months
DRUGPlacebo
po QD for 6 months
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sputum atypia participants with normal sputum cytology will be removed from the study) * Metaplasia or dysplasia on at least one bronchoscopy specimen * History of cigarette smoking ≥30 Pack Years * Quit smoking ≥1 year prior to study entry * Able to undergo bronchoscopy and helical computed tomography (CT) scanning of the chest * Able to swallow tablets
Exclusion criteria
* Blood clotting abnormalities * Current smoking within the past 1 year * Unwillingness to abstain from smoking while enrolled in the clinical trial or unwillingness to avoid significant second hand smoke exposure * Evidence for lung cancer or carcinoma in situ * Active cardiovascular disease * Current illicit drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage of Cells Staining Positive for Ki-67 in All Biopsy Specimens at Endpoint | Baseline, endpoint (up to 8 months) | The number of cells positively stained for Ki-67 (a marker of cellular proliferation) was enumerated and divided by the total number of cells in each specimen. The average Ki-67 labeling index (LI) (percentage of cells positively labeled with Ki-67) for all histological specimens was then calculated for each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Baseline through end of study (up to 32 months) | Summary tables of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enzastaurin Treatment with enzastaurin 500 milligrams (mg) orally (po), once daily (QD) given as 4 tablets (125 mg each). | 25 |
| Placebo Treatment with placebo po QD appearing identical to enzastaurin. | 15 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Enzastaurin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.84 years STANDARD_DEVIATION 6.06 | 66.97 years STANDARD_DEVIATION 4.67 | 66.89 years STANDARD_DEVIATION 5.51 |
| Eastern Cooperative Oncology Group (ECOG) Grade 0 | 19 Participants | 12 Participants | 31 Participants |
| Eastern Cooperative Oncology Group (ECOG) Grade 1 | 6 Participants | 3 Participants | 9 Participants |
| Evidence of Airway Obstruction Absence | 13 Participants | 11 Participants | 24 Participants |
| Evidence of Airway Obstruction Presence | 12 Participants | 4 Participants | 16 Participants |
| History of Stage I Non-small Cell Lung Cancer No | 24 Participants | 14 Participants | 38 Participants |
| History of Stage I Non-small Cell Lung Cancer Yes | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 24 Participants | 15 Participants | 39 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 25 Participants | 15 Participants | 40 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 19 Participants | 7 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 24 | 10 / 15 |
| serious Total, serious adverse events | 2 / 24 | 0 / 15 |
Outcome results
Primary
Change From Baseline in Percentage of Cells Staining Positive for Ki-67 in All Biopsy Specimens at Endpoint
The number of cells positively stained for Ki-67 (a marker of cellular proliferation) was enumerated and divided by the total number of cells in each specimen. The average Ki-67 labeling index (LI) (percentage of cells positively labeled with Ki-67) for all histological specimens was then calculated for each participant.
Time frame: Baseline, endpoint (up to 8 months)
Population: The number of participants analyzed was based on the efficacy population (EP). The EP included participants who met study criteria, were randomized to the study, and who had Ki-67 measurements from biopsy specimens.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzastaurin | Change From Baseline in Percentage of Cells Staining Positive for Ki-67 in All Biopsy Specimens at Endpoint | 3.74 percentage of cells with Ki-67 | Standard Deviation 11.68 |
| Placebo | Change From Baseline in Percentage of Cells Staining Positive for Ki-67 in All Biopsy Specimens at Endpoint | 6.15 percentage of cells with Ki-67 | Standard Deviation 11.08 |
p-value: 0.55695% CI: [-10.64, 5.83]2-sample pooled t-test
Secondary
Number of Participants With Adverse Events (AEs)
Summary tables of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.
Time frame: Baseline through end of study (up to 32 months)
Population: The number of participants analyzed was based on the safety population (SP). The SP included participants who received at least 1 dose of enzastaurin or placebo during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzastaurin | Number of Participants With Adverse Events (AEs) | SAEs | 2 Participants |
| Enzastaurin | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 24 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 10 Participants |