Breast Cancer
Conditions
Keywords
premenopausal breast cancer with chemotherapy-induced ovarian failure
Brief summary
Women with hormone-receptor positive breast cancer are typically treated with hormone therapy as part of their treatment after surgery. In the past few years it has been found that treatment with aromatase inhibitors is superior to tamoxifen in postmenopausal women. Tamoxifen is still used for premenopausal women, however, because aromatase inhibitors are not effective in women who have functioning ovaries. Some women are premenopausal at the time they are diagnosed with breast cancer, but then stop having menstrual periods when they are treated with chemotherapy. It is unclear if these women can also be treated safely with aromatase inhibitors. In this clinical trial the researchers will try to answer this question. Women with hormone receptor positive breast cancer who become postmenopausal with chemotherapy will be invited to participate in this study. Each woman will be treated with one of the aromatase inhibitors, anastrozole (Arimidex), and then carefully monitored to ensure that her ovaries do not start making estrogen. If her estrogen level remains low, then she will continued to be followed for 18 months. If the level increases to the level typically seen in premenopausal women, however, then she will stop taking part in this study. The study will also evaluate multiple factors that may help doctors predict who will tolerate the therapy without having their ovaries start making estrogen again. Some of the factors to be evaluated include other hormone levels (blood tests) as well as family history of early menopause (mother, sisters). In addition, changes in certain genes that affect how patients' bodies handle chemotherapy drugs will be tested to see if they affect whether or not patients recover ovarian function. Overall, the purpose of the study is to determine which patients who become postmenopausal from chemotherapy are likely to tolerate aromatase inhibitor treatment safely, and how often the patients' ovarian function needs to be tested during treatment.
Interventions
DRUGanastrozole
1 mg tablet by mouth once a day
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for this study: 1. You must be at least 18 years of age and not older than 60 years of age 2. You have breast cancer which was confined to the breast and lymph nodes under the arm, and have no evidence of cancer elsewhere 3. You must have had surgical removal of your tumor, and if indicated, radiation therapy must have been completed or planned 4. Your tumor must express estrogen and/or progesterone receptors 5. You must have had a menstrual period within 6 months before starting chemotherapy for your breast cancer. 6. You must have been treated with a chemotherapy regimen that includes cyclophosphamide (Cytoxan). Your menstrual periods must have stopped for at least 8 weeks starting during or after chemotherapy.
Exclusion criteria
You are not eligible to participate in this study if: 1\. Your ovaries have been surgically removed, treated with radiation therapy, or if you are taking medications (Zoladex™ or Lupron™) to block the function of your ovaries.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Women Who Recover Ovarian Function Within 12 Months of Al Monotherapy | 12 months | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at the University of Michigan, the Dana-Farber Cancer Institute, and Johns Hopkins University from 2008 until 2010.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Anastrozole Part 1 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. | 14 |
| Anastrozole Part 2 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. | 45 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 9 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Anastrozole Part 1 | Anastrozole Part 2 | Total |
|---|---|---|---|
| Age, Continuous | 46 years | 50 years | 50 years |
| Region of Enrollment United States | 14 participants | 45 participants | 59 participants |
| Sex: Female, Male Female | 14 Participants | 45 Participants | 59 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 53 / 59 |
| serious Total, serious adverse events | 2 / 59 |
Outcome results
Primary
The Number of Women Who Recover Ovarian Function Within 12 Months of Al Monotherapy
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.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anastrozole Part 1 | The Number of Women Who Recover Ovarian Function Within 12 Months of Al Monotherapy | 8 participants |
| Anastrozole Part 2 | The Number of Women Who Recover Ovarian Function Within 12 Months of Al Monotherapy | 13 participants |