Estrogen for Triple Negative Breast Cancer

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01083641
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 61.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effectiveness of Estradiol treatment for advanced breast cancer that is hormone receptor negative and Her2/neu negative. The study will also use tumor tissue from your original diagnosis or from a biopsy you may have had for your cancer to look at hormone receptors in the lab. The tissue left over from your previous surgery or a previous biopsy will be used for research tests to check whether a different estrogen receptor (estrogen receptor beta) is seen in the tumor and if that makes estrogen work better.

Condition or Disease	Intervention/Treatment	Phase
Female Breast Cancer	Drug: Estradiol	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of High Dose Estradiol in Metastatic Triple Negative Breast Cancer
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Estrogen Therapy Estrogen therapy	Drug: Estradiol; 10mg oral three times daily

Outcome Measures

Primary Outcome Measures

1. Determine Tumor Objective Response (OR) Rates [Up to 4 years]

   OR=complete response (CR) + partial response (PR) as defined by RECIST version 1.1, where CR=disappearance of all target lesions, and PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

1. Clinical Benefit (CB) [Up to 4 years]

   Defined as complete response, partial response, or stable disease at > 16 weeks

2. Progression-free Survival (PFS) [Up to 4 years]

3. Median Overall Survival (OS) [Up to 4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• histologically or cytologically confirmed breast cancer which is metastatic.

• A formalin-fixed paraffin embedded tumor block (preferred) or unstained slides must be available from either a prior biopsy of the primary tumor or a metastatic site. .

• Primary tumor or metastatic biopsy lacking estrogen and progesterone receptor and Her2 negative

• Patients must have measurable disease.

• Eastern Cooperative Oncology Group performance status 0-1.

• Patients with bone metastasis at baseline must agree to treatment with intravenous bisphosphonates

• Subjects may have had 0-4 lines of prior systemic chemotherapy or targeted therapy regimens administered for treatment of their metastatic breast cancer.

• Age >18 years

• Life expectancy of greater than 3 months.

• Patients must have adequate organ and marrow function as defined below:

Exclusion Criteria:

• systemic chemotherapies, targeted therapies or radiotherapy for their cancer within 2 weeks prior to entering the study

• Patients receiving any other investigational agents for breast cancer treatment.

• Patients with known brain metastases are excluded 3.2.4 History of allergic reactions attributed to compounds of similar chemical or biologic composition to estradiol.

• Patients with any condition of the gastrointestinal tract that is expected to result in an inability to take oral medication

• Dysfunctional or post-menopausal vaginal bleeding.

• Uncontrolled hypercalcemia/hypocalcemia

• Prior history of or active thrombophlebitis, cerebral vascular accident, myocardial infarction, deep venous thrombosis or pulmonary embolism.

• History of or active hepatic adenoma.

• Uncontrolled intercurrent illness

• Pregnant women are excluded from this study

• Patients with bone metastasis are excluded if they are unable to receive intravenous bisphosphonate therapy due to the risk for developing hypercalcemia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kari B Wisinski, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01083641
• Other Study ID Numbers: CO09711; H-2009-0172; NCI-2011-00618; A534260; SMPH\MEDICINE\HEM-ONC; P30CA014520
• First Posted: Mar 10, 2010
• Last Update Posted: Dec 9, 2019
• Last Verified: Mar 1, 2017

• Keywords provided by University of Wisconsin, Madison: Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Estradiol

Study Results

Participant Flow

Recruitment Details	This multicenter phase 2 study was conducted through the Wisconsin Oncology Network. Subjects were recruited from February 2010 through March 2013.

Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
Period Title: Overall Study
STARTED	17
COMPLETED	15
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.9
Sex: Female, Male (Count of Participants)
Female	17 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 11.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	14 82.4%
More than one race	0 0%
Unknown or Not Reported	1 5.9%
Region of Enrollment (participants) [Number]
United States	17 100%
Stage at Diagnosis (Count of Participants)
Stage I	3 17.6%
Stage II	9 52.9%
Stage III	4 23.5%
Stage IV	1 5.9%

Outcome Measures

1. Primary Outcome

Title	Determine Tumor Objective Response (OR) Rates
Description	OR=complete response (CR) + partial response (PR) as defined by RECIST version 1.1, where CR=disappearance of all target lesions, and PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	5.9 34.7%

2. Secondary Outcome

Title	Clinical Benefit (CB)
Description	Defined as complete response, partial response, or stable disease at > 16 weeks
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
Measure Participants	17
Complete Response	0 0%
Partial Response	1 5.9%
Stable Disease at > 16 weeks	1 5.9%
Stable Disease < 16 weeks	2 11.8%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
Measure Participants	17
Median (95% Confidence Interval) [months]	1.9

4. Secondary Outcome

Title	Median Overall Survival (OS)
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
Measure Participants	17
Median (95% Confidence Interval) [months]	7.6

Adverse Events

Time Frame	Adverse event data was collected for 4 years.
Adverse Event Reporting Description	Toxicity evaluations including history, examination, and laboratory analysis occurred on day 1 of each cycle.
Arm/Group Title	Estrogen Therapy
Arm/Group Description	Estrogen therapy Estradiol: 10mg oral three times daily
All Cause Mortality
	Estrogen Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Estrogen Therapy
	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)
Blood and lymphatic system disorders
Hemorrhage	1/17 (5.9%)	1
Cardiac disorders
Supraventricular and nodal arrhythmia	1/17 (5.9%)	1
Gastrointestinal disorders
Nausea	1/17 (5.9%)	2
Vomiting	2/17 (11.8%)	2
General disorders
Fatigue	1/17 (5.9%)	1
Fever	1/17 (5.9%)	1
Infections and infestations
Infection	1/17 (5.9%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	1/17 (5.9%)	1
Pain- back	1/17 (5.9%)	1
Nervous system disorders
Dizziness	1/17 (5.9%)	1
Headache	1/17 (5.9%)	1
Seizure	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/17 (11.8%)	2
Vascular disorders
Thrombosis/Thrombus/embolism	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Estrogen Therapy
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Edema: limb Count	6/17 (35.3%)	7
Hemoglobin Count	6/17 (35.3%)	7
Hemorrhage Count	5/17 (29.4%)	7
Leukocytes (total WBC) Count	3/17 (17.6%)	5
Lymphedema-related fibrosis Count	2/17 (11.8%)	2
Lymphopenia Count	1/17 (5.9%)	1
Neutrophils/granulocytes (ANC/AGC) Count	1/17 (5.9%)	1
Cardiac disorders
Hypertension Count	1/17 (5.9%)	1
Eye disorders
Vision-flashing lights/floaters Count	1/17 (5.9%)	2
Gastrointestinal disorders
Anorexia Count	4/17 (23.5%)	4
Constipation Count	4/17 (23.5%)	5
Diarrhea Count	1/17 (5.9%)	2
Distension/bloating, abdominal Count	3/17 (17.6%)	3
Dry mouth/salivary gland (xerostomia) Count	1/17 (5.9%)	1
Nausea Count	11/17 (64.7%)	12
Vomiting Count	5/17 (29.4%)	5
General disorders
Fatigue (asthenia, lethargy, malaise) Count	13/17 (76.5%)	23
Pain Count	14/17 (82.4%)	26
Weight gain Count	2/17 (11.8%)	2
Infections and infestations
Infection Count	4/17 (23.5%)	4
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia) Count	10/17 (58.8%)	11
Alkaline phosphatase Count	1/17 (5.9%)	1
ALT, SGPT (serum glutamic pyruvic transaminase) Count	2/17 (11.8%)	2
AST, SGOT(serum glutamic oxaloacetic transaminase) Count	3/17 (17.6%)	5
Calcium, serum-low (hypocalcemia) Count	3/17 (17.6%)	4
Creatinine Count	1/17 (5.9%)	1
Glucose, serum-high (hyperglycemia) Count	3/17 (17.6%)	3
Glucose, serum-low (hypoglycemia) Count	1/17 (5.9%)	1
Potassium, serum-low (hypokalemia) Count	2/17 (11.8%)	4
Sodium, serum-low (hyponatremia) Count	1/17 (5.9%)	1
Nervous system disorders
Confusion Count	1/17 (5.9%)	1
Dizziness Count	3/17 (17.6%)	3
Mood alteration - Anxiety Count	1/17 (5.9%)	1
Mood alteration - Depression Count	2/17 (11.8%)	2
Neuropathy: sensory Count	6/17 (35.3%)	8
Reproductive system and breast disorders
Vaginal discharge (non-infectious) Count	4/17 (23.5%)	4
Respiratory, thoracic and mediastinal disorders
Cough Count	5/17 (29.4%)	5
Dyspnea (shortness of breath) Count	5/17 (29.4%)	5
Pulmonary/Upper Respiratory - Other (Specify, __) Count	1/17 (5.9%)	1
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis) Count	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Dermal change lymphedema, phlebolymphedema Count	1/17 (5.9%)	1
Dermatology/Skin Count	1/17 (5.9%)	2
Hair loss/alopecia (scalp or body) Count	1/17 (5.9%)	1
Pruritus/itching Count	1/17 (5.9%)	1

Limitations/Caveats

[Not Specified]

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.