Trial Outcomes & Findings for Aromatase Inhibitors in Premenopausal Breast Cancer Patients With Chemotherapy-Induced Ovarian Failure (NCT NCT00555477)
NCT ID: NCT00555477
Last Updated: 2014-06-19
Results Overview
In part 1 ovarian function recurrence is defined as one estradiol value \>20 pg/ml or two consecutive values \>10 pg/ml. In part 2 ovarian function recurrence is defined as a \>75% increase in estradiol levels over prior if prior value was 15-30 pg/ml, or one estradiol value \>30 pg/ml, or three consecutive values \>20 pg/ml.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
69 participants
Primary outcome timeframe
12 months
Results posted on
2014-06-19
Participant Flow
Subjects were recruited at the University of Michigan, the Dana-Farber Cancer Institute, and Johns Hopkins University from 2008 until 2010.
69 patients were enrolled however only 59 patients began treatment with anastrozole. Patients that were enrolled and found to have estradiol concentrations greater than 20 pg/ml were not treated.
Participant milestones
| Measure |
Anastrozole Part 1
In the initial version of the clinical trial (designated part 1), subjects were required to have serum estradiol and FSH (Follicle-stimulating hormone) concentrations within the postmenopausal range according to local institutional guidelines within 28 days of enrollment. Subjects taking tamoxifen at the time of screening were only required to have postmenopausal serum estradiol concentrations. Subjects were treated with anastrozole, 1 mg orally daily.
|
Anastrozole Part 2
During the conduct of the trial the study was amended to change the eligibility criteria because of difficulties with the estradiol assay. Subjects enrolled after the amendment were required to sign consent and then have an average baseline estradiol concentration of ≤20 pg/ml in order to be considered eligible.
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
45
|
|
Overall Study
COMPLETED
|
12
|
32
|
|
Overall Study
NOT COMPLETED
|
2
|
13
|
Reasons for withdrawal
| Measure |
Anastrozole Part 1
In the initial version of the clinical trial (designated part 1), subjects were required to have serum estradiol and FSH (Follicle-stimulating hormone) concentrations within the postmenopausal range according to local institutional guidelines within 28 days of enrollment. Subjects taking tamoxifen at the time of screening were only required to have postmenopausal serum estradiol concentrations. Subjects were treated with anastrozole, 1 mg orally daily.
|
Anastrozole Part 2
During the conduct of the trial the study was amended to change the eligibility criteria because of difficulties with the estradiol assay. Subjects enrolled after the amendment were required to sign consent and then have an average baseline estradiol concentration of ≤20 pg/ml in order to be considered eligible.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
9
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Physician Decision
|
1
|
2
|
Baseline Characteristics
Aromatase Inhibitors in Premenopausal Breast Cancer Patients With Chemotherapy-Induced Ovarian Failure
Baseline characteristics by cohort
| Measure |
Anastrozole Part 1
n=14 Participants
In the initial version of the clinical trial (designated part 1), subjects were required to have serum estradiol and FSH concentrations within the postmenopausal range according to local institutional guidelines within 28 days of enrollment. Subjects taking tamoxifen at the time of screening were only required to have postmenopausal serum estradiol concentrations. Subjects were treated with anastrozole, 1 mg orally daily.
|
Anastrozole Part 2
n=45 Participants
Analysis of the first 18 subjects enrolled revealed a greater than expected discontinuation of AI therapy because of elevated serum estradiol concentrations. Discontinuation was believed to be primarily due to greater than expected variability in the assay as opposed to true recovery of ovarian function. Therefore, the protocol was amended. Subjects with an average baseline estradiol concentration of ≤20 pg/ml were considered eligible for part 2 and initiated treatment with anastrozole 1 mg orally daily.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46 years
n=93 Participants
|
50 years
n=4 Participants
|
50 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=93 Participants
|
45 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=93 Participants
|
45 participants
n=4 Participants
|
59 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 12 monthsIn part 1 ovarian function recurrence is defined as one estradiol value \>20 pg/ml or two consecutive values \>10 pg/ml. In part 2 ovarian function recurrence is defined as a \>75% increase in estradiol levels over prior if prior value was 15-30 pg/ml, or one estradiol value \>30 pg/ml, or three consecutive values \>20 pg/ml.
Outcome measures
| Measure |
Anastrozole Part 1
n=14 Participants
In the initial version of the clinical trial (designated part 1), subjects were required to have serum estradiol and FSH concentrations within the postmenopausal range according to local institutional guidelines within 28 days of enrollment. Subjects taking tamoxifen at the time of screening were only required to have postmenopausal serum estradiol concentrations. Subjects were treated with anastrozole, 1 mg orally daily.
|
Anastrozole Part 2
n=45 Participants
Analysis of the first 18 subjects enrolled revealed a greater than expected discontinuation of AI therapy because of elevated serum estradiol concentrations. Discontinuation was believed to be primarily due to greater than expected variability in the assay as opposed to true recovery of ovarian function. Therefore, the protocol was amended. Subjects with an average baseline estradiol concentration of ≤20 pg/ml were considered eligible for part 2 and initiated treatment with anastrozole 1 mg orally daily.
|
|---|---|---|
|
The Number of Women Who Recover Ovarian Function Within 12 Months of Al Monotherapy
|
8 participants
|
13 participants
|
Adverse Events
Anastrozole
Serious events: 2 serious events
Other events: 53 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Anastrozole
n=59 participants at risk
anastrozole: 1 mg tablet by mouth once a day
|
|---|---|
|
Infections and infestations
Infection Grade 3 or 4 neutrophils
|
1.7%
1/59 • Number of events 1 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
1.7%
1/59 • Number of events 1 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
Other adverse events
| Measure |
Anastrozole
n=59 participants at risk
anastrozole: 1 mg tablet by mouth once a day
|
|---|---|
|
General disorders
Fatigue
|
23.7%
14/59 • Number of events 15 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Psychiatric disorders
Insomnia
|
25.4%
15/59 • Number of events 16 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify)
|
8.5%
5/59 • Number of events 5 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
6.8%
4/59 • Number of events 4 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
8.5%
5/59 • Number of events 7 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Vascular disorders
Hot flashes/flushes
|
30.5%
18/59 • Number of events 19 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Reproductive system and breast disorders
Hemorrhage, Vagina
|
13.6%
8/59 • Number of events 10 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
General disorders
Edema: limb
|
13.6%
8/59 • Number of events 8 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Musculoskeletal and connective tissue disorders
Joint-function
|
13.6%
8/59 • Number of events 8 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Specify)
|
10.2%
6/59 • Number of events 9 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Nervous system disorders
Dizziness
|
8.5%
5/59 • Number of events 7 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Nervous system disorders
Mood alteration
|
18.6%
11/59 • Number of events 12 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Nervous system disorders
Neuropathy: sensory
|
11.9%
7/59 • Number of events 8 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
General disorders
Pain-Abdomen
|
10.2%
6/59 • Number of events 7 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Reproductive system and breast disorders
Pain-Breast
|
6.8%
4/59 • Number of events 5 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Musculoskeletal and connective tissue disorders
Pain-Limb
|
13.6%
8/59 • Number of events 9 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Nervous system disorders
Pain-Head
|
6.8%
4/59 • Number of events 4 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Musculoskeletal and connective tissue disorders
Pain-Joint
|
39.0%
23/59 • Number of events 29 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Musculoskeletal and connective tissue disorders
Pain-Muscle
|
11.9%
7/59 • Number of events 8 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
General disorders
Pain - Other (Specify)
|
6.8%
4/59 • Number of events 6 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
|
Reproductive system and breast disorders
Vaginal dryness
|
23.7%
14/59 • Number of events 15 • All Adverse Events (AEs) will be captured while each patient is taking study medication and for 30 days after the patient discontinues study medication and/or trial participation.
|
Additional Information
Dr. Norah Lynn Henry
University of Michigan Comprehensive Cancer Center
Phone: 734-936-4991
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place