A Trial of Placebo Versus Enzastaurin for Lung Cancer Prevention in Former Smokers

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00414960
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Enzastaurin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase IIB Randomized, Placebo-Controlled, Double-Blind Study of Enzastaurin HCL (LY317615) for Lung Cancer Prevention in Former Smokers
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzastaurin Treatment with enzastaurin 500 milligrams (mg) orally (po) once daily (QD) given as 4 tablets (125 mg each).	Drug: Enzastaurin; 500 mg po QD for 6 months; Other Names: LY317615
Placebo Comparator: Placebo Treatment with placebo po QD appearing identical to enzastaurin.	Drug: Placebo; po QD for 6 months

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tampa	Florida	United States	33612

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00414960
• Other Study ID Numbers: 10723; H6Q-MC-S009; NCT00387816
• First Posted: Dec 22, 2006
• Last Update Posted: Sep 21, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Eli Lilly and Company: Healthy; Prevention
• Additional relevant MeSH terms: Lung Neoplasms

Study Results

Participant Flow

Arm/Group Title	Enzastaurin	Placebo
Arm/Group Description	Treatment with enzastaurin 500 milligrams (mg) orally (po), once daily (QD) given as 4 tablets (125 mg each).	Treatment with placebo po QD appearing identical to enzastaurin.
Period Title: Overall Study
STARTED	25	15
Received at Least One Dose of Study Drug	24	15
COMPLETED	18	14
NOT COMPLETED	7	1

Baseline Characteristics

Arm/Group Title	Enzastaurin	Placebo	Total
Arm/Group Description	Treatment with enzastaurin 500 milligrams (mg) orally (po), once daily (QD) given as 4 tablets (125 mg each).	Treatment with placebo po QD appearing identical to enzastaurin.	Total of all reporting groups
Overall Participants	25	15	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.84 (6.06)	66.97 (4.67)	66.89 (5.51)
Sex: Female, Male (Count of Participants)
Female	6 24%	8 53.3%	14 35%
Male	19 76%	7 46.7%	26 65%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	24 96%	15 100%	39 97.5%
Hispanic	1 4%	0 0%	1 2.5%
Region of Enrollment (Count of Participants)
United States	25 100%	15 100%	40 100%
Evidence of Airway Obstruction (Count of Participants)
Absence	13 52%	11 73.3%	24 60%
Presence	12 48%	4 26.7%	16 40%
Eastern Cooperative Oncology Group (ECOG) (Count of Participants)
Grade 0	19 76%	12 80%	31 77.5%
Grade 1	6 24%	3 20%	9 22.5%
History of Stage I Non-small Cell Lung Cancer (Count of Participants)
Yes	1 4%	1 6.7%	2 5%
No	24 96%	14 93.3%	38 95%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Percentage of Cells Staining Positive for Ki-67 in All Biopsy Specimens at Endpoint
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Enzastaurin	Placebo
Arm/Group Description	Treatment with enzastaurin 500 milligrams (mg) orally (po), once daily (QD) given as 4 tablets (125 mg each).	Treatment with placebo po QD appearing identical to enzastaurin.
Measure Participants	21	13
Mean (Standard Deviation) [percentage of cells with Ki-67]	3.74 (11.68)	6.15 (11.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.556
	Comments	P-value is for comparison of change from baseline between enzastaurin and placebo group.
	Method	2-sample pooled t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.40
	Confidence Interval	(2-Sided) 95%; -10.64 to 5.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.04
	Estimation Comments	Using placebo as a reference group, the mean difference = enzastaurin minus placebo.

2. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Enzastaurin	Placebo
Arm/Group Description	Treatment with enzastaurin 500 milligrams (mg) orally (po), once daily (QD) given as 4 tablets (125 mg each).	Treatment with placebo po QD appearing identical to enzastaurin.
Measure Participants	24	15
SAEs	2 8%	0 0%
Other Non-Serious AEs	24 96%	10 66.7%

Adverse Events

Arm/Group Title	Enzastaurin		Placebo
Arm/Group Description	Treatment with enzastaurin 500 milligrams (mg) orally (po), once daily (QD) given as 4 tablets (125 mg each).		Treatment with placebo po QD appearing identical to enzastaurin.
All Cause Mortality
	Enzastaurin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Enzastaurin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		0/15 (0%)
Cardiac disorders
Bradycardia	1/24 (4.2%)	1	0/15 (0%)	0
Vascular disorders
Deep vein thrombosis	1/24 (4.2%)	1	0/15 (0%)	0
Hypotension	1/24 (4.2%)	1	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	Enzastaurin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/24 (100%)		10/15 (66.7%)
Blood and lymphatic system disorders
Lymphadenopathy	0/24 (0%)	0	1/15 (6.7%)	1
Cardiac disorders
Conduction disorder	0/24 (0%)	0	1/15 (6.7%)	1
Extrasystoles	0/24 (0%)	0	1/15 (6.7%)	1
Sinus bradycardia	2/24 (8.3%)	2	0/15 (0%)	0
Supraventricular extrasystoles	2/24 (8.3%)	3	0/15 (0%)	0
Ear and labyrinth disorders
Hearing impaired	0/24 (0%)	0	1/15 (6.7%)	1
Eye disorders
Eye pain	0/24 (0%)	0	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal distension	2/24 (8.3%)	2	0/15 (0%)	0
Abdominal pain upper	0/24 (0%)	0	1/15 (6.7%)	1
Diarrhoea	4/24 (16.7%)	4	2/15 (13.3%)	2
Dry mouth	2/24 (8.3%)	2	0/15 (0%)	0
Dyspepsia	1/24 (4.2%)	1	1/15 (6.7%)	1
General disorders
Fatigue	1/24 (4.2%)	1	2/15 (13.3%)	2
Local swelling	0/24 (0%)	0	1/15 (6.7%)	1
Oedema peripheral	2/24 (8.3%)	2	0/15 (0%)	0
Infections and infestations
Urinary tract infection	0/24 (0%)	0	1/15 (6.7%)	1
Viral infection	0/24 (0%)	0	1/15 (6.7%)	1
Injury, poisoning and procedural complications
Stress fracture	0/24 (0%)	0	1/15 (6.7%)	1
Investigations
Alanine aminotransferase increased	2/24 (8.3%)	3	1/15 (6.7%)	1
Aspartate aminotransferase increased	1/24 (4.2%)	1	1/15 (6.7%)	1
Blood alkaline phosphatase increased	0/24 (0%)	0	1/15 (6.7%)	3
Blood creatinine increased	2/24 (8.3%)	2	0/15 (0%)	0
Electrocardiogram QT prolonged	3/24 (12.5%)	5	1/15 (6.7%)	1
Haemoglobin decreased	6/24 (25%)	7	0/15 (0%)	0
Haemoglobin increased	0/24 (0%)	0	1/15 (6.7%)	1
Urine colour abnormal	4/24 (16.7%)	4	0/15 (0%)	0
Metabolism and nutrition disorders
Hypercalcaemia	2/24 (8.3%)	2	1/15 (6.7%)	1
Hyperglycaemia	5/24 (20.8%)	5	1/15 (6.7%)	1
Hyperkalaemia	8/24 (33.3%)	13	1/15 (6.7%)	1
Hypoglycaemia	2/24 (8.3%)	2	0/15 (0%)	0
Hyponatraemia	6/24 (25%)	9	1/15 (6.7%)	1
Nervous system disorders
Dizziness	2/24 (8.3%)	2	0/15 (0%)	0
Psychiatric disorders
Insomnia	0/24 (0%)	0	1/15 (6.7%)	1
Sleep disorder	0/24 (0%)	0	1/15 (6.7%)	1
Renal and urinary disorders
Chromaturia	2/24 (8.3%)	2	0/15 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/24 (8.3%)	2	0/15 (0%)	0
Dyspnoea	2/24 (8.3%)	2	0/15 (0%)	0
Rhinitis allergic	0/24 (0%)	0	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders
Rash	2/24 (8.3%)	3	0/15 (0%)	0
Vascular disorders
Hypertension	1/24 (4.2%)	1	1/15 (6.7%)	1

Limitations/Caveats

The planned enrollment for the study was 186 participants, but enrollment was terminated early due to the difficulty of accruing participants once 40 were enrolled into the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.