Trial Outcomes & Findings for Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ (NCT NCT01439711)

Results Overview

Mean total MRI FTV change from baseline to month 3 (V3): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V3 was calculated by subtracting the total MRI FTV measured (i.e. the sum over all lesions present with MRI FTV measurements) at 3 months from the total MRI FTV measured at baseline. For V3 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

up to 3 months from start of treatment

Results posted on

2018-03-27

Participant Flow

Participant milestones

Participant milestones
Measure	Letrozole + MRI Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Overall Study STARTED	108
Overall Study COMPLETED	68
Overall Study NOT COMPLETED	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Letrozole + MRI Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Overall Study Ineligible	13
Overall Study Cancel	3
Overall Study Progression Prior to Beginning Tx	1
Overall Study Adverse Event	5
Overall Study Withdrawal by Subject	3
Overall Study Progression During Active Tx	3
Overall Study Noncompliance	3
Overall Study No MRI	9

Baseline Characteristics

Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Letrozole + MRI n=68 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Age, Continuous	63.2 years STANDARD_DEVIATION 8.03 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	68 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 3 months from start of treatment

Mean total MRI FTV change from baseline to month 3 (V3): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V3 was calculated by subtracting the total MRI FTV measured (i.e. the sum over all lesions present with MRI FTV measurements) at 3 months from the total MRI FTV measured at baseline. For V3 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=68 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 3 (V3)	-1.93 cubic centimeters Interval -2.87 to -0.98

PRIMARY outcome

Timeframe: up to 6 months from start of treatment

Mean total MRI FTV change from baseline to month 6 (V6): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V6 was calculated by subtracting the total MRI FTV measured at 6 months from the total MRI FTV measured at baseline. For V6 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=68 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 6 (V6)	-1.82 cubic centimeters Interval -2.75 to -0.9

SECONDARY outcome

Timeframe: 3-months

To ascertain the change in maximum tumor diameter from baseline to 3 months (D3) the same methods as in Primary outcome #1 will be used but on diameter instead of volume. For patients with more than one lesion longest diameter measurement, the sum of all lesion longest diameter measurements was calculated.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=68 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Mean Total MRI Tumor Diameter Change From Baseline to Month 3	-10.3 millimeters Interval -13.94 to -6.66

SECONDARY outcome

Timeframe: 6-months

Population: Patients who completed a mammogram at both time points (baseline and month 6) with measurements available were included in this analysis.

Change in maximum diameter at 6-months based on mammographic measurement (MD6) will be estimated using the methods in Primary Outcome #1, but using the mammographic measurements instead.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=52 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Change in Maximum Diameter at 6-months Based on Mammographic Measurement (MD6)	-3.31 millimeters Interval -7.0 to 0.38

SECONDARY outcome

Timeframe: up to 6 months

Population: Patients who underwent surgery were included in this analysis.

Rate of Mastectomy will be estimated as the number of mastectomies divided by the number of surgeries. A 95% confidence interval will be constructed using exact binomial methods. Rate of Lumpectomy will be estimated as the number of lumpectomies divided by the number of surgeries. A 95% confidence interval will be constructed using exact binomial methods.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=59 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Type of Primary Surgery (Mastectomy or Lumpectomy) Rate of Mastectomy	7 percentage of surgeries Interval 2.0 to 16.0
Type of Primary Surgery (Mastectomy or Lumpectomy) Rate of Lumpectomy	93 percentage of surgeries Interval 84.0 to 98.0

SECONDARY outcome

Timeframe: 3-months and 6-months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months post-surgery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3-months and 6-months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3-months and 6-months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months post surgery

Population: Patients who had completed the study and had an Adverse Event Form submitted were included in this analysis.

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=67 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Allergic reaction	31 Participants
Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Cholesterol high	7 Participants
Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Gastrointestinal disorder	2 Participants
Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Hot flashes	1 Participants

SECONDARY outcome

Timeframe: 6 months

Mean total MRI tumor diameter change from baseline to month 6: To ascertain the change in maximum tumor diameter from baseline to 6 months (D6) the same methods as in Primary Outcome #2 will be used but on diameter instead of volume.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=68 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Mean Total MRI Tumor Diameter Change From Baseline to Month 6	-16.66 millimeters Interval -21.09 to -12.23

SECONDARY outcome

Timeframe: 6 months

To ascertain the change in maximum tumor diameter from baseline to 6 months (D6) the same methods as in Primary outcome #2 will be used but on diameter instead of volume. For patients with more than one lesion longest diameter measurement, the sum of all lesion longest diameter measurements was calculated.

Outcome measures

Outcome measures
Measure	Letrozole + MRI n=68 Participants Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Mean Total MRI Tumor Diameter Change From Baseline to Month 6	-16.66 millimeters Interval -21.09 to -12.23

Adverse Events

Letrozole + MRI

Serious events: 2 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Letrozole + MRI n=90 participants at risk Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Cardiac disorders Heart failure	1.1% 1/90 • Number of events 1
Cardiac disorders Restrictive cardiomyopathy	1.1% 1/90 • Number of events 1
General disorders Fever	1.1% 1/90 • Number of events 1
Metabolism and nutrition disorders Hypokalemia	1.1% 1/90 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/90 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	1.1% 1/90 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1.1% 1/90 • Number of events 1
Vascular disorders Hypertension	2.2% 2/90 • Number of events 2

Other adverse events

Other adverse events
Measure	Letrozole + MRI n=90 participants at risk Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	5.6% 5/90 • Number of events 5
Gastrointestinal disorders Nausea	3.3% 3/90 • Number of events 4
General disorders Fatigue	1.1% 1/90 • Number of events 2
General disorders Fever	1.1% 1/90 • Number of events 1
Immune system disorders Allergic reaction	3.3% 3/90 • Number of events 5
Injury, poisoning and procedural complications Fracture	3.3% 3/90 • Number of events 3
Investigations Cholesterol high	4.4% 4/90 • Number of events 6
Musculoskeletal and connective tissue disorders Arthralgia	47.8% 43/90 • Number of events 87
Musculoskeletal and connective tissue disorders Back pain	1.1% 1/90 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	21.1% 19/90 • Number of events 28
Musculoskeletal and connective tissue disorders Osteoporosis	5.6% 5/90 • Number of events 8
Nervous system disorders Headache	1.1% 1/90 • Number of events 1
Psychiatric disorders Depression	1.1% 1/90 • Number of events 1
Psychiatric disorders Insomnia	1.1% 1/90 • Number of events 1
Vascular disorders Hot flashes	55.6% 50/90 • Number of events 103
Vascular disorders Hypertension	17.8% 16/90 • Number of events 25

Additional Information

E. Shelley Hwang MD MPH

Duke University Medical Center

Phone: 919-684-6849

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place