Estrogen in Postmenopausal Women With ER Positive Metastatic Breast Cancer After Failure of Sequential Endocrine Therapy
Study Details
Study Description
Brief Summary
This trial seeks to confirm the response rate for estrace treatment in a patients with hormone receptor positive metastatic breast cancer heavily pre-treated with modern endocrine therapies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Prior to the current standard of care utilizing estrogen deprivation or antiestrogen therapy to treat hormonally sensitive breast cancers, treatment with pharmacologic doses of estrogen was a common technique used to treat post-menopausal women with hormone sensitive metastatic disease that resulted in durable responses with regression of disease. A randomized trial comparing tamoxifen and pharmacologic doses of estrogen demonstrated similar rates of response with long-term follow-up data confirming a survival benefit for those treated with the estrogen preparation. Additional data has shown that post-menopausal women with hormonally sensitive tumors that have progressed on prior endocrine therapies responded to treatment with pharmacologic doses of estrogen. These data, coupled with pre-clinical data that postmenopausal levels of estrogen can be used to cause apoptosis (programmed cell death within the tumor) and tumor regression in exhaustively treated endocrine resistant disease form the rationale for the proposed clinical trial. This trial seeks to confirm the response rate for estrace treatment in a patient population heavily pre-treated with modern endocrine therapies.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Estrace & Anastrozole Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered |
Drug: Estrace
Estrace 10 mg three times daily will be administered for 3 months.
Drug: Anastrozole
After 3 months of estrace, patients who do not have evidence of disease progression will then be switched to received Anastrozole 1 mg daily as long as their disease benefits from this treatment
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival [6 months]
Progression free survival is defined as the time from assignment of treatment to the time of disease progression or death from any cause
Secondary Outcome Measures
- Response Rate [6 months]
Response rate was defined per RECIST version 1.0. In this study, response rate was defined as including patients with either a complete response (complete disappearance of all target lesions with changes confirmed by repeat assessments performed no less than 4 weeks after the criteria for response was first met) or a partial response (at least 30% decrease in the sum of the longest diameter of the target lesions)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed estrogen and/or progesterone receptor-positive breast cancer metastatic breast cancer
-
Clinically determined evaluable disease
-
Post-menopausal woman
-
Previous clinical benefit from prior anti-estrogen therapies and subsequent failure of at least 2 prior endocrine therapies.
-
May have had chemotherapy for adjuvant &/or metastatic disease.
-
May have had radiation therapy but not to the only site of disease.
-
Ecog performance status </= 2.
-
Life expectancy of > 6 months
Exclusion Criteria:
-
Chemotherapy or radiotherapy within 1 week of beginning treatment in the clinical trial
-
Brain metastasis
-
Prior history of or active thrombophlebitis, deep venous thrombosis or pulmonary embolus
-
Current vaginal bleeding
-
Hypercalcemia or hypocalcemia
-
History of or active hepatic adenoma
-
No other malignancies within the past 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Georgetown University Medical Center | Washington | District of Columbia | United States | 20057 |
| 2 | Cooper Cancer Institute | Voorhees | New Jersey | United States | 08043 |
| 3 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
Sponsors and Collaborators
- Georgetown University
Investigators
- Principal Investigator: Claudine Isaacs, M.D., Lombardi Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FER-BR-030
- W81XWH-06-1-0590
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Estrace & Anastrozole |
|---|---|
| Arm/Group Description | Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered Estrace: Estrace 10 mg three times daily will be administered for 3 months. Anastrozole: After 3 months of estrace, patients who do not have evidence of disease progression will then be switched to received Anastrozole 1 mg daily as long as their disease benefits from this treatment |
| Period Title: Overall Study | |
| STARTED | 11 |
| COMPLETED | 8 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Estrace & Anastrozole |
|---|---|
| Arm/Group Description | Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered |
| Overall Participants | 11 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
7
63.6%
|
| >=65 years |
4
36.4%
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
64
|
| Sex: Female, Male (Count of Participants) | |
| Female |
11
100%
|
| Male |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
9.1%
|
| White |
10
90.9%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
11
100%
|
Outcome Measures
| Title | Progression Free Survival |
|---|---|
| Description | Progression free survival is defined as the time from assignment of treatment to the time of disease progression or death from any cause |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Estrace & Anastrozole |
|---|---|
| Arm/Group Description | Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered Estrace: Estrace 10 mg three times daily will be administered for 3 months. Anastrozole: After 3 months of estrace, patients who do not have evidence of disease progression will then be switched to received Anastrozole 1 mg daily as long as their disease benefits from this treatment |
| Measure Participants | 11 |
| Count of Participants [Participants] |
7
63.6%
|
| Title | Response Rate |
|---|---|
| Description | Response rate was defined per RECIST version 1.0. In this study, response rate was defined as including patients with either a complete response (complete disappearance of all target lesions with changes confirmed by repeat assessments performed no less than 4 weeks after the criteria for response was first met) or a partial response (at least 30% decrease in the sum of the longest diameter of the target lesions) |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Estrace & Anastrozole |
|---|---|
| Arm/Group Description | Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered Estrace: Estrace 10 mg three times daily will be administered for 3 months. Anastrozole: After 3 months of estrace, patients who do not have evidence of disease progression will then be switched to received Anastrozole 1 mg daily as long as their disease benefits from this treatment |
| Measure Participants | 11 |
| Count of Participants [Participants] |
2
18.2%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Estrace & Anastrozole | |
| Arm/Group Description | Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered Estrace: Estrace 10 mg three times daily will be administered for 3 months. Anastrozole: After 3 months of estrace, patients who do not have evidence of disease progression will then be switched to received Anastrozole 1 mg daily as long as their disease benefits from this treatment | |
All Cause Mortality |
||
| Estrace & Anastrozole | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Estrace & Anastrozole | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/11 (18.2%) | |
| Gastrointestinal disorders | ||
| Anal Hemorrhage | 1/11 (9.1%) | 1 |
| Metabolism and nutrition disorders | ||
| Hypercalcemia | 1/11 (9.1%) | 11 |
Other (Not Including Serious) Adverse Events |
||
| Estrace & Anastrozole | ||
| Affected / at Risk (%) | # Events | |
| Total | 11/11 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 6/11 (54.5%) | 11 |
| Neutropenia | 1/11 (9.1%) | 1 |
| Lymphopenia | 7/11 (63.6%) | 9 |
| Cardiac disorders | ||
| Hypertension | 2/11 (18.2%) | 5 |
| Gastrointestinal disorders | ||
| Nausea | 8/11 (72.7%) | 10 |
| Emesis | 3/11 (27.3%) | 3 |
| Diarrhea | 2/11 (18.2%) | 2 |
| Dysphagia | 3/11 (27.3%) | 3 |
| Constipation | 4/11 (36.4%) | 5 |
| Anorexia | 4/11 (36.4%) | 5 |
| Abdominal pain | 3/11 (27.3%) | 3 |
| General disorders | ||
| Fatigue | 9/11 (81.8%) | 12 |
| Chills | 3/11 (27.3%) | 3 |
| Infections and infestations | ||
| Rhinitis | 4/11 (36.4%) | 7 |
| Infection | 2/11 (18.2%) | 2 |
| Investigations | ||
| Aspartate aminotransferase elevation | 5/11 (45.5%) | 5 |
| Alkaline phosphotase elevation | 7/11 (63.6%) | 15 |
| Alanine aminotransferase elevation | 4/11 (36.4%) | 7 |
| Metabolism and nutrition disorders | ||
| Hypoalbuminemia | 7/11 (63.6%) | 12 |
| Hyperglycemia | 9/11 (81.8%) | 21 |
| Hypercalcemia | 3/11 (27.3%) | 3 |
| Hypocalcemia | 2/11 (18.2%) | 6 |
| Musculoskeletal and connective tissue disorders | ||
| Bone pain | 3/11 (27.3%) | 3 |
| Weakness generalized | 4/11 (36.4%) | 5 |
| Musculoskeletal pain | 4/11 (36.4%) | 11 |
| Nervous system disorders | ||
| Dizziness | 4/11 (36.4%) | 4 |
| Neuropathy | 2/11 (18.2%) | 4 |
| Headache | 4/11 (36.4%) | 4 |
| Psychiatric disorders | ||
| Anxiety | 2/11 (18.2%) | 2 |
| Insomnia | 4/11 (36.4%) | 5 |
| Depression | 2/11 (18.2%) | 2 |
| Reproductive system and breast disorders | ||
| Vaginal bleeding | 6/11 (54.5%) | 7 |
| Breast pain | 6/11 (54.5%) | 7 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 5/11 (45.5%) | 14 |
| Dypsnea | 1/11 (9.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 1/11 (9.1%) | 4 |
| Rash | 1/11 (9.1%) | 4 |
| Vascular disorders | ||
| Lymphedema | 2/11 (18.2%) | 3 |
| Edema | 4/11 (36.4%) | 5 |
| Hot flashes | 3/11 (27.3%) | 3 |
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. Claudine Isaacs |
|---|---|
| Organization | Georgetown University |
| Phone | 2024443677 |
| isaacsc@georgetown.edu |
- FER-BR-030
- W81XWH-06-1-0590