Aromatase Inhibitors in Premenopausal Breast Cancer Patients With Chemotherapy-Induced Ovarian Failure
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: anastrozole
|
Drug: anastrozole
1 mg tablet by mouth once a day
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
To be eligible for this study:
-
You must be at least 18 years of age and not older than 60 years of age
-
You have breast cancer which was confined to the breast and lymph nodes under the arm, and have no evidence of cancer elsewhere
-
You must have had surgical removal of your tumor, and if indicated, radiation therapy must have been completed or planned
-
Your tumor must express estrogen and/or progesterone receptors
-
You must have had a menstrual period within 6 months before starting chemotherapy for your breast cancer.
-
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:
- 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sidney Kimmel Comprehensive Center at Johns Hopkins | Baltimore | Maryland | United States | 21231-2410 |
| 2 | Dana-Farber Cancer Center | Boston | Massachusetts | United States | 02115 |
| 3 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- University of Michigan Rogel Cancer Center
Investigators
- Principal Investigator: Norah L. Henry, M.D., Ph.D., University of Michigan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UMCC 2007.044
- HUM 12443
Study Results
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 Detail | 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. |
| Arm/Group Title | Anastrozole Part 1 | Anastrozole Part 2 |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 14 | 45 |
| COMPLETED | 12 | 32 |
| NOT COMPLETED | 2 | 13 |
Baseline Characteristics
| Arm/Group Title | Anastrozole Part 1 | Anastrozole Part 2 | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 of all reporting groups |
| Overall Participants | 14 | 45 | 59 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
46
|
50
|
50
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
14
100%
|
45
100%
|
59
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
14
100%
|
45
100%
|
59
100%
|
Outcome Measures
| Title | The Number of Women Who Recover Ovarian Function Within 12 Months of Al Monotherapy |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Anastrozole Part 1 | Anastrozole Part 2 |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 14 | 45 |
| Number [participants] |
8
57.1%
|
13
28.9%
|
Adverse Events
| Time Frame | 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. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Anastrozole | |
| Arm/Group Description | anastrozole: 1 mg tablet by mouth once a day | |
All Cause Mortality |
||
| Anastrozole | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Anastrozole | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/59 (3.4%) | |
| Infections and infestations | ||
| Infection Grade 3 or 4 neutrophils | 1/59 (1.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Fracture | 1/59 (1.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Anastrozole | ||
| Affected / at Risk (%) | # Events | |
| Total | 53/59 (89.8%) | |
| General disorders | ||
| Fatigue | 14/59 (23.7%) | 15 |
| Edema: limb | 8/59 (13.6%) | 8 |
| Pain-Abdomen | 6/59 (10.2%) | 7 |
| Pain - Other (Specify) | 4/59 (6.8%) | 6 |
| Musculoskeletal and connective tissue disorders | ||
| Joint-function | 8/59 (13.6%) | 8 |
| Musculoskeletal/Soft Tissue - Other (Specify) | 6/59 (10.2%) | 9 |
| Pain-Limb | 8/59 (13.6%) | 9 |
| Pain-Joint | 23/59 (39%) | 29 |
| Pain-Muscle | 7/59 (11.9%) | 8 |
| Nervous system disorders | ||
| Dizziness | 5/59 (8.5%) | 7 |
| Mood alteration | 4/59 (6.8%) | 4 |
| Mood alteration | 11/59 (18.6%) | 12 |
| Neuropathy: sensory | 7/59 (11.9%) | 8 |
| Pain-Head | 4/59 (6.8%) | 4 |
| Psychiatric disorders | ||
| Insomnia | 15/59 (25.4%) | 16 |
| Reproductive system and breast disorders | ||
| Hemorrhage, Vagina | 8/59 (13.6%) | 10 |
| Pain-Breast | 4/59 (6.8%) | 5 |
| Vaginal dryness | 14/59 (23.7%) | 15 |
| Skin and subcutaneous tissue disorders | ||
| Dermatology/Skin - Other (Specify) | 5/59 (8.5%) | 5 |
| Hair loss/alopecia (scalp or body) | 4/59 (6.8%) | 4 |
| Rash/desquamation | 5/59 (8.5%) | 7 |
| Vascular disorders | ||
| Hot flashes/flushes | 18/59 (30.5%) | 19 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Dr. Norah Lynn Henry |
|---|---|
| Organization | University of Michigan Comprehensive Cancer Center |
| Phone | 734-936-4991 |
| norahh@umich.edu |
- UMCC 2007.044
- HUM 12443