RFCLET2: Effect of Aromatase Inhibitors on Breast Magnetic Resonance Imaging (MRI)

• Sponsor: Mount Sinai Hospital, Canada (Other)
• Overall Status: Completed
• CT.gov ID: NCT01129622
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 23
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study is a primary investigation to determine the usefulness and safety of a short course of a relatively high dose of letrozole (a medication used to decrease the female hormone estrogen which is produced locally inside the breast after menopause) in improving the performance of of breast MRI (Magnetic Resonance Imaging). The inhibition of estrogen in the breast by letrozole might help better identifying of suspicious areas in the breast and could assist radiologists in distinguishing between benign breast areas and cancer tissue. This might help reducing the rate of call backs and unnecessary biopsies for patients. We expect to enroll 20 healthy postmenopausal women in this study.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: letrozole	Phase 2

Detailed Description

A breast MRI will be performed in the standard way for diagnosis and to serve as a baseline. A second MRI will be performed within a month and following administration of letrozole 12.5 mg daily for three days to reduce breast estrogen levels and in anticipation of lowering breast gadolinium dye uptake.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Phase II Study of the Effect of Acute Aromatase Inhibition on Breast MRI Postmenopausal Women
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Letrozole, Breast enhancement, Safety Single arm of healthy postmenopausal women who received baseline diagnostic MRI will receive letrozole of 12.5 mg/day orally for three successive days. A second post treatment breast MRI is done right after receiving the three days of letrozole treatment and within one month after the first MRI .	Drug: letrozole; Letrozole (12.5 mg/day ) which is higher than the dose routinely used for therapeutic indications is given for a brief duration (3 successive days) aiming to promote acute aromatase inhibition suitable for pre-diagnostic regimens.; Other Names: Femara TM Novartis Pharmaceuticals Canada Inc., Dorval, QC

Outcome Measures

Primary Outcome Measures

1. Number of Women With Reduced Breast Parenchymal Enhancement [One month MRI study after letrozole compared to baseline MRI study, both with gadolinium enhancement]

   Image analysis was done using the e-film workstation. A region of interest was selected in all images. The signal intensity of enhancement was recorded and the relative enhancement (percentage of increase in signal intensity) was calculated as (SIc - SI)/SI × 100, where SI and SIc are the precontrast and the postcontrast signal intensities, respectively. Relative enhancement was compared at the baseline MRI study and the after one month MRI study for all participants.

Secondary Outcome Measures

1. Number of Participants Developed Adverse Effects of 12.5 mg of Letrozole [Three days plus One Week following medication]

   The number of participants who developed short term hypoestrogenic side effects or other adverse effects of letrozole during the intake of the medication or in the following week.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women are eligible to participate if they are 40 years or older and have been menopausal (had no menstrual bleeding during the past 12 months)

Exclusion Criteria:

• History of bilateral mastectomy, osteoporosis or renal impairment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Hospital	Toronto	Ontario	Canada	M5T 3H7

Sponsors and Collaborators

• Mount Sinai Hospital, Canada

Investigators

• Principal Investigator: Robert F Casper, MD, Mount Sinai Hopsital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Casper, Professor, Obstetrics and Gynecology, Mount Sinai Hospital, Canada
• ClinicalTrials.gov Identifier: NCT01129622
• Other Study ID Numbers: CFWH-AI1
• First Posted: May 24, 2010
• Last Update Posted: May 1, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Robert Casper, Professor, Obstetrics and Gynecology, Mount Sinai Hospital, Canada: Letrozole; Breast MRI; Postmenopausal women
• Additional relevant MeSH terms: Letrozole

Study Results

Participant Flow

Recruitment Details	16 women over age 40 on hormone therapy were recruited. No previous abnormal breast imaging.

Arm/Group Title	Letrozole, Breast Enhancement, Safety
Arm/Group Description	Single arm of healthy postmenopausal women to have two breast MRI (baseline and post-treatment). Letrozole of 12.5 mg/day is given for three successive days just prior to the second MRI.
Period Title: Overall Study
STARTED	16
COMPLETED	14
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Letrozole, Breast Enhancement, Safety
Arm/Group Description	Single arm of healthy postmenopausal women to have two breast MRI (baseline and post-treatment). Letrozole of 12.5 mg/day is given for three successive days just prior to the second MRI.
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (11)
Sex: Female, Male (Count of Participants)
Female	16 100%
Male	0 0%
Region of Enrollment (participants) [Number]
Canada	16 100%

Outcome Measures

1. Primary Outcome

Title	Number of Women With Reduced Breast Parenchymal Enhancement
Description	Image analysis was done using the e-film workstation. A region of interest was selected in all images. The signal intensity of enhancement was recorded and the relative enhancement (percentage of increase in signal intensity) was calculated as (SIc - SI)/SI × 100, where SI and SIc are the precontrast and the postcontrast signal intensities, respectively. Relative enhancement was compared at the baseline MRI study and the after one month MRI study for all participants.
Time Frame	One month MRI study after letrozole compared to baseline MRI study, both with gadolinium enhancement

Outcome Measure Data

Analysis Population Description

All participants who completed two MRIs were analysed. Percentage reduction in breast enhancement compared to baseline was determined.

Arm/Group Title	Letrozole, Breast Enhancement, Safety
Arm/Group Description	Single arm of healthy postmenopausal women to have two breast MRI (baseline and post-treatment). Letrozole of 12.5 mg/day is given for three successive days just prior to the second MRI.
Measure Participants	14
Number [Number of participants]	7 43.8%

2. Secondary Outcome

Title	Number of Participants Developed Adverse Effects of 12.5 mg of Letrozole
Description	The number of participants who developed short term hypoestrogenic side effects or other adverse effects of letrozole during the intake of the medication or in the following week.
Time Frame	Three days plus One Week following medication

Outcome Measure Data

Analysis Population Description

All entered subjects

Arm/Group Title	Adverse Events
Arm/Group Description	Hypo-estrogenic side effects
Measure Participants	14
Number [Number of participants]	3 18.8%

Adverse Events

Time Frame	10 months
Adverse Event Reporting Description	Subject report of adverse events prior to second MRI.
Arm/Group Title	Letrozole, Breast Enhancement, Safety
Arm/Group Description	Single arm of healthy postmenopausal women to have two breast MRI (baseline and post-treatment). Letrozole of 12.5 mg/day is given for three successive days just prior to the second MRI.
All Cause Mortality
	Letrozole, Breast Enhancement, Safety
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Letrozole, Breast Enhancement, Safety
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Letrozole, Breast Enhancement, Safety
	Affected / at Risk (%)	# Events
Total	3/14 (21.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/14 (14.3%)
Nervous system disorders
Headache	1/14 (7.1%)

Limitations/Caveats

The small sample size is a limitation.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.