Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention

• ClinicalTrials.gov Identifier: NCT00285857
• Recruitment Status: Terminated
• First Posted: February 2, 2006
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Sponsor: Stanford University
• Information provided by (Responsible Party): James Ford, Stanford University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer
• Intervention: Drug: Lovastatin
• Enrollment: 30

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Lovastatin 80 mg/Day
Arm/Group Description	Lovastatin 80 mg/day given as 40 mg orally twice per day
Period Title: Overall Study
Started	30
Completed	26
Not Completed	4
Reason Not Completed
Withdrawal by Subject	2
Inadequate initial breast cytology	1
Adverse Event	1

Baseline Characteristics

Arm/Group Title		Lovastatin
Arm/Group Description		Lovastatin: 80 mg; 40 mg orally twice per day
Overall Number of Baseline Participants		30
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	30 100.0%
	>=65 years	0 0.0%
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	30 participants
		45; (25 to 62)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants
	Female	30 100.0%
	Male	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	30 participants
		30

Outcome Measures

1. Primary Outcome

Title	Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day
Description	Assessed on that basis of pre- and post-treatment evaluation with RPFNA (random periareolar fine needle aspiration). All subjects received a prescription for lovastatin 80 mg/day, to be taken as 40 mg twice-a-day. Cytology was qualitatively and quantitatively, using the Masood semiquantitative scale to assign a number to each specimen, with higher numbers indicating increasing degrees of abnormality, as follows: 06-10 Non-proliferative breast disease (NPBD) 11-14 Proliferative breast disease without atypia (PBD-A) 15-18 Proliferative breast disease with atypia (PBD+A) 19-24 Carcinoma in situ and invasive cancer (CIS/IC) If no cells could be obtained after multiple RPFNA attempts, the classification was acellular. Change from NPBD to PBD-A was considered Unfavorable. Change from NPBD to Acellular was considered Equivocal. Change from PBD-A to NPBD was considered Favorable.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants either at least one of the following:

• Deleterious germline mutation in BRCA1, BRCA2, CDH1, or TP53
• Lifetime breast cancer risk of breast cancer of 20 % as estimated by the Claus model
• Personal history of estrogen receptor andprogesterone receptor-negative breast cancer.

Arm/Group Title	Baseline Non-proliferative Breast Disease (NPBD)	Baseline Proliferative Breast Disease Without Atypia (PBD-A)	Baseline Proliferative Breast Disease With Atypia (PBD+A)	Baseline Carcinoma in Situ or Invasive Cancer (CIS/IC)	Baseline Biopsy Acellular
Arm/Group Description:	Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of non-proliferative breast disease	Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease without atypia	Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease with atypia	Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of carcinoma in situ or invasive cancer	Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) generated a sample that was acellular
Overall Number of Participants Analyzed	13	12	0	0	1
Measure Type: Number; Unit of Measure: participants
Post-treatment NPBD	8	5			1
Post-treatment PBD-A	2	7			0
Post-treatment PBD+A	0	0			0
Post-treatment CIS/IC	0	0			0
Post-treatment biopsy acellular	3	0			0

2. Secondary Outcome

Title	Change in Mammographic Density Before and After Treatment With Lovastatin 80 mg/Day
Description	Bilateral mammography was performed at study entry (before lovastatin therapy) and at study conclusion (after lovastatin therapy) . Mammograms were assessed for a decline in mean breast density, using the American College of Radiology Breast Imaging Reporting and Data System (BI-RAD) composition system for mammographic density assessment. Category 0 Need additional imaging evaluation; Negative; Benign; Probably benign; Suspicious abnormality; Highly suggestive of malignancy; Known biopsy-proven malignancy
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Outcome reported as the change in mean mammographic density with standard deviation (SD) of the post-treatment measurements.

Arm/Group Title	Lovastatin 80 mg/Day
Arm/Group Description:	Lovastatin 80 mg/day given as 40 mg orally twice per day
Overall Number of Participants Analyzed	30
Mean (Standard Deviation); Unit of Measure: BI-RADS
	-0.10 (1.08)

3. Secondary Outcome

Title	Change in Total Cholesterol After Treatment With Lovastatin 80 mg/Day
Description	[Not Specified]
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lovastatin 80 mg/Day
Arm/Group Description:	Lovastatin 80 mg/day given as 40 mg orally twice per day
Overall Number of Participants Analyzed	25
Mean (Standard Deviation); Unit of Measure: mg/dL
	-8 (45.7)

4. Secondary Outcome

Title	Change in Low Density Lipoprotein (LDL) After Treatment With Lovastatin 80 mg/Day
Description	[Not Specified]
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Change in mean of LDL level, with standard deviation of the values at

Arm/Group Title	Lovastatin 80 mg/Day
Arm/Group Description:	Lovastatin 80 mg/day given as 40 mg orally twice per day
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	-6 (32.1)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lovastatin
Arm/Group Description	Lovastatin: 80 mg; 40 mg orally twice per day
All-Cause Mortality
	Lovastatin
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lovastatin
	Affected / at Risk (%)	# Events
Total	0/30 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Lovastatin
	Affected / at Risk (%)	# Events
Total	3/30 (10.00%)
Gastrointestinal disorders
Dyspepsia *	1/30 (3.33%)	1
Musculoskeletal and connective tissue disorders
Myalgia *	1/30 (3.33%)	1
Arthralgia *	1/30 (3.33%)	1
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: James M. Ford
• Organization: Stanford University
• Phone: (650) 498-6689
• EMail: jmf@stanford.edu

Publications of Results:

Vinayak S, Schwartz EJ, Jensen K, Lipson J, Alli E, McPherson L, Fernandez AM, Sharma VB, Staton A, Mills MA, Schackmann EA, Telli ML, Kardashian A, Ford JM, Kurian AW. A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk. Breast Cancer Res Treat. 2013 Nov;142(2):389-98. doi: 10.1007/s10549-013-2739-z. Epub 2013 Oct 29.

• Responsible Party: James Ford, Stanford University
• ClinicalTrials.gov Identifier: NCT00285857
• Other Study ID Numbers: IRB-13732; BRSNSTU0010 ( Other Identifier: OnCore ); 95505 ( Other Identifier: Stanford University Alternate IRB Approval Number )
• First Submitted: January 31, 2006
• First Posted: February 2, 2006
• Results First Submitted: November 17, 2016
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017