Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Clinical Benefit Rate (CR Plus PR Plus SD) [ Time Frame: 24 weeks after start of treatment ] [ Designated as safety issue: No ]
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.
- Progression-free Survival (PFS) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Overall Survival (OS) [ Time Frame: Until patient death ] [ Designated as safety issue: No ]
|Study Start Date:||August 2004|
|Study Completion Date:||August 2014|
|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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00324259
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|United States, North Carolina|
|University of North Carolina Breast Clinic|
|Chapel Hill, North Carolina, United States, 27599|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Case Western University|
|Cleveland, Ohio, United States, 44106|
|Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Matthew Ellis, M.D., Ph.D.||Washington University School of Medicine|