Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer
This study has been completed.
Information provided by (Responsible Party):
Washington University School of Medicine
First received: May 8, 2006
Last updated: January 29, 2015
Last verified: January 2015
This study aims to examine whether estradiol is an appropriate for future Phase 3 studies as second or third line endocrine treatment. In addition the protocol explores several approaches to enhance the safety of estrogen therapy, including the establishment of the efficacy of a lower dose than that currently recommended and through the early identification of non-responders to avoid drug exposure in patients who are unlikely to benefit to estrogen treatment.
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Randomized Study of Physiological (6 mg Daily) and High Dose (30 mg Daily) Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer
Primary Outcome Measures:
- Clinical Benefit Rate (CR Plus PR Plus SD) [ Time Frame: 24 weeks after start of treatment ]
Complete response (CR) + partial response (PR) + stable disease (SD) using RECIST 1.0
CR = disappearance of all target lesions
PR = at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter
SD = neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for progressive disease
SD is defined as lack of disease progression by 24 weeks.
Secondary Outcome Measures:
- Progression-free Survival (PFS) [ Time Frame: Up to 48 weeks ]
Defined as the time from treatment initiation to disease progression or death.
Time of last observation for patients remaining in the study and the time at which dose reductions, study drug termination, and withdrawal of consent occurred were treated as censored data.
Indicated as number of participants who had not progressed at 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Progression per RECIST 1.0 = at least a 20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
- Quality of Life [ Time Frame: Baseline and Day 28 ]
Surveyed using a 6 item estrogen adverse effect questionnaire (headaches, bloating, breast tenderness, retention of fluid, nausea, and vomiting).
Used a 5-point scale ranging from 0 (not at all) to 4 (very much).
The scores from the 6 estrogen adverse effect items were summed to produce a single score, ranging from 0-24, with higher scores indicating higher adverse effects.
- Quality of Life (FACT-B Mean Score) [ Time Frame: Day 28 ]
Surveyed using the multidimensional Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire
The FACT-B (version 4) questionnaire consists of 36 items with five-point scale, ranging from 0-4, where a total score ranges from 0-144 and higher scores indicate better QoL. The total FACT-B score is the sum of scores for five subscales including: physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and specific breast cancer concerns (9 items).
- Frequency of Response to Re-treatment With the Same Aromatase Inhibitor That Immediately Preceded Treatment With Estradiol on Protocol. [ Time Frame: 12 weeks post-treatment termination ]
Best overall response
- Frequency of Response to Re-treatment With Estradiol for Patients Who Have a Secondary Response to an Aromatase Inhibitor After the First Response to Estradiol. [ Time Frame: Every 3 months ]
- Overall Survival (OS) [ Time Frame: Until patient death ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||March 2011 (Final data collection date for primary outcome measure)
Active Comparator: Arm 1 (6 mg estradiol)
6 mg of estradiol daily (2 mg tid).
Active Comparator: Arm 2 (30 mg estradiol)
30 mg of estradiol. (10 mg tid)
The purpose of this study is to compare the effects of two doses (6 mg and 30 mg) of Estradiol, a type of estrogen. This and other forms of estrogen used at doses much higher than those used for postmenopausal hormone replacement therapy have been shown to cause tumor growth stabilization or shrinkage in patients with breast cancer.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- Postmenopausal women with advanced hormone receptor positive (ER and or PgR) breast cancer, has received prior treatment with an aromatase inhibitor in the advanced disease setting, and experienced at least 24 weeks of progression free survival. As long as the patient experienced an aromatase inhibitor response as defined this way, she is still eligible even if she has received further lines of endocrine therapy, which may include other aromatase inhibitors or tamoxifen, even if these subsequent lines of treatment were unsuccessful (see below for permitted chemotherapy and trastuzumab therapy).
- Patients with CNS involvement with metastatic breast cancer or life threatening lymphangitic or large volume lung or liver disease that threatens organ function.
- Patients with history of deep venous thrombosis, pulmonary embolism, stroke, acute myocardial infarction, congestive cardiac failure, untreated hypertension.
- Ischemic changes on a baseline EKG or other evidence of ischemic heart disease.
- Undiagnosed abnormal genital bleeding
- Untreated cholelithiasis
- Fasting serum triglycerides greater than 400. Patients should be treated and triglycerides controlled prior to study entry.
- Treatment with fulvestrant within 12 months of study initiation (fulvestrant has been shown to antagonize estradiol induced apoptosis in preclinical models (5).
- The patient's only qualifying lesion (s) have been previously irradiated or are scheduled for irradiation following study entry.
- Severe or uncontrolled concomitant disease from other causes.
- EGOG Performance status 3 or 4.
- The patient has previous malignancies other than breast cancer except a) adequately treated in situ carcinoma of the cervix, b) localized basal or squamous cell carcinoma of the skin c) any previous malignancy treated with curative intent with a recurrence risk of less than 30%.
- The patient is unable to understand the informed consent or is unlikely to be compliant with the protocol.
- More than one line of palliative chemotherapy for advanced disease.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00324259
|University of Chicago
|Chicago, Illinois, United States, 60637 |
|Washington University School of Medicine
|St. Louis, Missouri, United States, 63110 |
|Memorial Sloan-Kettering Cancer Center
|New York, New York, United States, 10021 |
|University of North Carolina Breast Clinic
|Chapel Hill, North Carolina, United States, 27599 |
|Duke University Medical Center
|Durham, North Carolina, United States, 27710 |
|Case Western University
|Cleveland, Ohio, United States, 44106 |
|Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University
|Cleveland, Ohio, United States, 44195 |
Washington University School of Medicine
||Matthew Ellis, M.D., Ph.D.
||Washington University School of Medicine
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA. 2009 Aug 19;302(7):774-80. doi: 10.1001/jama.2009.1204.
||Washington University School of Medicine
History of Changes
|Other Study ID Numbers:
04-0412 / 201108392
|Study First Received:
||May 8, 2006
|Results First Received:
||October 8, 2014
||January 29, 2015
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on February 20, 2017
Neoplasms by Site
Estradiol 17 beta-cypionate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Reproductive Control Agents
Contraceptive Agents, Female