Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Reproductive Control Agents

Estradiol

Hormones

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Polyestradiol phosphate

Estrogens

Hormone Antagonists

Matthew Ellis, M.D., Ph.D.

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.

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.

Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer

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

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.

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.

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.

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).

Washington University School of Medicine

Arm 1 (6 mg Estradiol)

Arm 2 (30 mg Estradiol)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Bone/soft tissue

Visceral

Both

Site

Negative

Positive

Estrogen receptor status

Progesterone receptor status

The slight imbalance in numbers assigned to the 2 groups was a because of yearly data and safety monitoring, which led to early closure of the 30mg group for toxicity concerns after 32 patients had been enrolled.

Dr. Matthew Ellis

Complete response (CR)

Partial response (PR)

Stable disease (SD)

CR+PR+SD

Clinical Benefit Rate (CR Plus PR Plus SD)

12 weeks (no progression)

24 weeks (no progression)

36 weeks (no progression)

48 weeks (no progression)

Progression-free Survival (PFS)

Baseline

Day 28

27 out of 34 participants in Arm 1 and 22 out of 32 participants in Arm 2 completed both the baseline and Day 28 (4 week) 6 item adverse effect questionnaire.

Quality of Life

25 out of 34 participants in Arm 1 and 23 out of 32 participants completed the FACT-B questionnaire at Day 28 (4 weeks).

Quality of Life (FACT-B Mean Score)

Partial response

Stable disease

Progressive disease

Only offered to patients experiencing clinical benefit on estradiol.

Frequency of Response to Re-treatment With the Same Aromatase Inhibitor That Immediately Preceded Treatment With Estradiol on Protocol.

At the time that the study was powered there was not any information on any patients who were re-treated with estradiol after having a secondary response to a aromatase inhibitor after the first response to estradiol.

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.

This outcome measure was not analyzed as the overall survival was not reported.

Overall Survival (OS)

Complete response

Arm 1 = 6 mg of estradiol daily (2 mg tid).

Arm 2 = 30 mg of estradiol. (10 mg tid)

Arm 1 (6 mg Estradiol) and Arm 2 (30 mg Estradiol)

The data was combined as the outcome was not based on comparison of the two groups but comparing the overall FDG-PET/CT metabolic flare to the overall responses.

10 participants were not evaluable because early toxicity prevented response assessment and the PET data was not considered technically adequate or not available in 8 participants.

Metabolic Flare on FDG-PET/CT as Compared to Response

Overall Study

Spots Global Cancer Trial Database for Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer

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