Trial Outcomes & Findings for Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer (NCT NCT00324259)
NCT ID: NCT00324259
Last Updated: 2015-02-16
Results Overview
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.
COMPLETED
PHASE2
66 participants
24 weeks after start of treatment
2015-02-16
Participant Flow
The study opened to participant enrollment on 08/03/2004 and closed to participant enrollment on 02/19/2008.
Participant milestones
| Measure |
Arm 1 (6 mg Estradiol)
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Overall Study
STARTED
|
34
|
32
|
|
Overall Study
COMPLETED
|
34
|
32
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Arm 1 (6 mg Estradiol)
n=34 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=32 Participants
30 mg of estradiol. (10 mg tid)
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.7 years
n=5 Participants
|
59.5 years
n=7 Participants
|
57.1 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
34 participants
n=5 Participants
|
32 participants
n=7 Participants
|
66 participants
n=5 Participants
|
|
Site
Bone/soft tissue
|
18 participants
n=5 Participants
|
13 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Site
Visceral
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Site
Both
|
11 participants
n=5 Participants
|
14 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Estrogen receptor status
Negative
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Estrogen receptor status
Positive
|
33 participants
n=5 Participants
|
32 participants
n=7 Participants
|
65 participants
n=5 Participants
|
|
Progesterone receptor status
Negative
|
8 participants
n=5 Participants
|
6 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Progesterone receptor status
Positive
|
26 participants
n=5 Participants
|
26 participants
n=7 Participants
|
52 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 weeks after start of treatmentComplete 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.
Outcome measures
| Measure |
Arm 1 (6 mg Estradiol)
n=34 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=32 Participants
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Clinical Benefit Rate (CR Plus PR Plus SD)
Partial response (PR)
|
3 participants
|
1 participants
|
|
Clinical Benefit Rate (CR Plus PR Plus SD)
Complete response (CR)
|
0 participants
|
0 participants
|
|
Clinical Benefit Rate (CR Plus PR Plus SD)
Stable disease (SD)
|
7 participants
|
8 participants
|
|
Clinical Benefit Rate (CR Plus PR Plus SD)
CR+PR+SD
|
10 participants
|
9 participants
|
SECONDARY outcome
Timeframe: Up to 48 weeksDefined 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.
Outcome measures
| Measure |
Arm 1 (6 mg Estradiol)
n=34 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=32 Participants
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Progression-free Survival (PFS)
12 weeks (no progression)
|
30 participants
|
20 participants
|
|
Progression-free Survival (PFS)
24 weeks (no progression)
|
13 participants
|
9 participants
|
|
Progression-free Survival (PFS)
36 weeks (no progression)
|
7 participants
|
6 participants
|
|
Progression-free Survival (PFS)
48 weeks (no progression)
|
6 participants
|
3 participants
|
SECONDARY outcome
Timeframe: Baseline and Day 28Population: 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.
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.
Outcome measures
| Measure |
Arm 1 (6 mg Estradiol)
n=27 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=22 Participants
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Quality of Life
Baseline
|
0.47 units on a scale
Standard Deviation 0.48
|
0.46 units on a scale
Standard Deviation 0.59
|
|
Quality of Life
Day 28
|
0.70 units on a scale
Standard Deviation 0.55
|
0.92 units on a scale
Standard Deviation 0.87
|
SECONDARY outcome
Timeframe: Day 28Population: 25 out of 34 participants in Arm 1 and 23 out of 32 participants completed the FACT-B questionnaire at Day 28 (4 weeks).
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).
Outcome measures
| Measure |
Arm 1 (6 mg Estradiol)
n=25 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=23 Participants
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Quality of Life (FACT-B Mean Score)
|
109.5 units on a scale
Standard Deviation 17.9
|
106.9 units on a scale
Standard Deviation 21.2
|
SECONDARY outcome
Timeframe: 12 weeks post-treatment terminationPopulation: Only offered to patients experiencing clinical benefit on estradiol.
Best overall response
Outcome measures
| Measure |
Arm 1 (6 mg Estradiol)
n=4 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=3 Participants
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Frequency of Response to Re-treatment With the Same Aromatase Inhibitor That Immediately Preceded Treatment With Estradiol on Protocol.
Partial response
|
1 participants
|
1 participants
|
|
Frequency of Response to Re-treatment With the Same Aromatase Inhibitor That Immediately Preceded Treatment With Estradiol on Protocol.
Stable disease
|
1 participants
|
0 participants
|
|
Frequency of Response to Re-treatment With the Same Aromatase Inhibitor That Immediately Preceded Treatment With Estradiol on Protocol.
Progressive disease
|
2 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Every 3 monthsPopulation: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Until patient deathPopulation: This outcome measure was not analyzed as the overall survival was not reported.
Outcome measures
Outcome data not reported
POST_HOC outcome
Timeframe: Baseline and 24 hours after administration of the first dose of estradiolPopulation: 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.
Outcome measures
| Measure |
Arm 1 (6 mg Estradiol)
n=46 Participants
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Metabolic Flare on FDG-PET/CT as Compared to Response
Complete response
|
0 participants
|
—
|
|
Metabolic Flare on FDG-PET/CT as Compared to Response
Partial response
|
3 participants
|
—
|
|
Metabolic Flare on FDG-PET/CT as Compared to Response
Stable disease
|
9 participants
|
—
|
|
Metabolic Flare on FDG-PET/CT as Compared to Response
Progressive disease
|
3 participants
|
—
|
Adverse Events
Arm 1 (6 mg Estradiol)
Arm 2 (30 mg Estradiol)
Serious adverse events
| Measure |
Arm 1 (6 mg Estradiol)
n=34 participants at risk
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=32 participants at risk
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
5.9%
2/34
|
3.1%
1/32
|
|
Renal and urinary disorders
Acute renal failure
|
0.00%
0/34
|
3.1%
1/32
|
|
Musculoskeletal and connective tissue disorders
Arm pain
|
0.00%
0/34
|
3.1%
1/32
|
|
Nervous system disorders
CNS ischemia
|
2.9%
1/34
|
0.00%
0/32
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/34
|
6.2%
2/32
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.9%
1/34
|
0.00%
0/32
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/34
|
6.2%
2/32
|
|
Gastrointestinal disorders
Diarrhea
|
5.9%
2/34
|
3.1%
1/32
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.8%
3/34
|
3.1%
1/32
|
|
Eye disorders
Eye pain
|
0.00%
0/34
|
3.1%
1/32
|
|
General disorders
Fatigue
|
0.00%
0/34
|
3.1%
1/32
|
|
General disorders
Fever
|
5.9%
2/34
|
0.00%
0/32
|
|
Gastrointestinal disorders
GI hemorrhage
|
2.9%
1/34
|
0.00%
0/32
|
|
Nervous system disorders
Headache
|
0.00%
0/34
|
6.2%
2/32
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/34
|
3.1%
1/32
|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/34
|
3.1%
1/32
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/34
|
3.1%
1/32
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Nausea
|
5.9%
2/34
|
9.4%
3/32
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.9%
1/34
|
0.00%
0/32
|
|
Investigations
Neutropenia
|
0.00%
0/34
|
3.1%
1/32
|
|
General disorders
Pain
|
0.00%
0/34
|
3.1%
1/32
|
|
Surgical and medical procedures
Perforated viscus
|
0.00%
0/34
|
3.1%
1/32
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.9%
1/34
|
3.1%
1/32
|
|
Infections and infestations
Pneumonia
|
2.9%
1/34
|
0.00%
0/32
|
|
Vascular disorders
Thrombosis/embolism
|
2.9%
1/34
|
0.00%
0/32
|
|
Eye disorders
Vison loss
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
2/34
|
9.4%
3/32
|
|
Metabolism and nutrition disorders
Weight loss
|
0.00%
0/34
|
3.1%
1/32
|
Other adverse events
| Measure |
Arm 1 (6 mg Estradiol)
n=34 participants at risk
6 mg of estradiol daily (2 mg tid).
|
Arm 2 (30 mg Estradiol)
n=32 participants at risk
30 mg of estradiol. (10 mg tid)
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
5.9%
2/34
|
9.4%
3/32
|
|
Investigations
Alkaline phosphtase
|
5.9%
2/34
|
6.2%
2/32
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.9%
1/34
|
0.00%
0/32
|
|
Metabolism and nutrition disorders
Anorexia
|
17.6%
6/34
|
25.0%
8/32
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
35.3%
12/34
|
43.8%
14/32
|
|
Gastrointestinal disorders
Ascites
|
2.9%
1/34
|
0.00%
0/32
|
|
Nervous system disorders
Ataxia
|
2.9%
1/34
|
0.00%
0/32
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
52.9%
18/34
|
56.2%
18/32
|
|
Reproductive system and breast disorders
Breast pain
|
20.6%
7/34
|
40.6%
13/32
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
2.9%
1/34
|
0.00%
0/32
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
2.9%
1/34
|
0.00%
0/32
|
|
Reproductive system and breast disorders
Change in libido
|
8.8%
3/34
|
3.1%
1/32
|
|
Respiratory, thoracic and mediastinal disorders
Chest congestion
|
2.9%
1/34
|
0.00%
0/32
|
|
Cardiac disorders
Chest pain
|
5.9%
2/34
|
9.4%
3/32
|
|
Gastrointestinal disorders
Constipation
|
32.4%
11/34
|
25.0%
8/32
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.5%
8/34
|
21.9%
7/32
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Dental pain
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Diarrhea
|
17.6%
6/34
|
21.9%
7/32
|
|
Nervous system disorders
Dizziness
|
17.6%
6/34
|
25.0%
8/32
|
|
Gastrointestinal disorders
Dry mouth
|
5.9%
2/34
|
3.1%
1/32
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.9%
1/34
|
0.00%
0/32
|
|
Gastrointestinal disorders
Dyspepsia/heartburn
|
26.5%
9/34
|
28.1%
9/32
|
|
Gastrointestinal disorders
Dysphagia
|
2.9%
1/34
|
3.1%
1/32
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
23.5%
8/34
|
28.1%
9/32
|
|
Blood and lymphatic system disorders
Edema
|
20.6%
7/34
|
31.2%
10/32
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/34
|
6.2%
2/32
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
2.9%
1/34
|
3.1%
1/32
|
|
General disorders
Fatigue
|
64.7%
22/34
|
56.2%
18/32
|
|
General disorders
Fever
|
11.8%
4/34
|
6.2%
2/32
|
|
Reproductive system and breast disorders
Groin pain
|
0.00%
0/34
|
3.1%
1/32
|
|
Nervous system disorders
Headache
|
20.6%
7/34
|
37.5%
12/32
|
|
Renal and urinary disorders
Hematuria
|
2.9%
1/34
|
0.00%
0/32
|
|
Blood and lymphatic system disorders
Hemoglobin
|
14.7%
5/34
|
37.5%
12/32
|
|
Skin and subcutaneous tissue disorders
Hirsuitism
|
5.9%
2/34
|
6.2%
2/32
|
|
Skin and subcutaneous tissue disorders
Hives
|
0.00%
0/34
|
3.1%
1/32
|
|
Vascular disorders
Hot flashes
|
14.7%
5/34
|
21.9%
7/32
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.9%
1/34
|
3.1%
1/32
|
|
Investigations
Hypercholesterolemia
|
5.9%
2/34
|
6.2%
2/32
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.9%
2/34
|
6.2%
2/32
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/34
|
3.1%
1/32
|
|
Skin and subcutaneous tissue disorders
Hyperpigmentation
|
0.00%
0/34
|
3.1%
1/32
|
|
Vascular disorders
Hypertension
|
5.9%
2/34
|
3.1%
1/32
|
|
Investigations
Hypertriglyceridemia
|
17.6%
6/34
|
34.4%
11/32
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
8.8%
3/34
|
18.8%
6/32
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
5.9%
2/34
|
9.4%
3/32
|
|
Metabolism and nutrition disorders
Hypokalemia
|
2.9%
1/34
|
3.1%
1/32
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.9%
2/34
|
12.5%
4/32
|
|
Infections and infestations
Infection without neutropenia
|
14.7%
5/34
|
31.2%
10/32
|
|
Psychiatric disorders
Insomnia
|
29.4%
10/34
|
34.4%
11/32
|
|
Musculoskeletal and connective tissue disorders
Leg pain
|
0.00%
0/34
|
3.1%
1/32
|
|
Investigations
Leukocytes
|
5.9%
2/34
|
0.00%
0/32
|
|
Investigations
Lymphopenia
|
14.7%
5/34
|
21.9%
7/32
|
|
Nervous system disorders
Migraine
|
0.00%
0/34
|
6.2%
2/32
|
|
Psychiatric disorders
Mood alteration - anxeity
|
32.4%
11/34
|
15.6%
5/32
|
|
Psychiatric disorders
Mood alteration - depression
|
14.7%
5/34
|
9.4%
3/32
|
|
Nervous system disorders
Motor neuropathy
|
0.00%
0/34
|
3.1%
1/32
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
47.1%
16/34
|
28.1%
9/32
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.9%
1/34
|
0.00%
0/32
|
|
Gastrointestinal disorders
Nausea
|
55.9%
19/34
|
50.0%
16/32
|
|
Investigations
Neutrophils
|
5.9%
2/34
|
0.00%
0/32
|
|
Cardiac disorders
Palpitations
|
2.9%
1/34
|
3.1%
1/32
|
|
Reproductive system and breast disorders
Pelvic pain
|
5.9%
2/34
|
0.00%
0/32
|
|
Skin and subcutaneous tissue disorders
Pigmentation change
|
2.9%
1/34
|
3.1%
1/32
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/34
|
9.4%
3/32
|
|
Renal and urinary disorders
Proteinuria
|
2.9%
1/34
|
0.00%
0/32
|
|
Skin and subcutaneous tissue disorders
Pruritis/itching
|
14.7%
5/34
|
6.2%
2/32
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.9%
2/34
|
6.2%
2/32
|
|
Investigations
SGOT (AST)
|
2.9%
1/34
|
3.1%
1/32
|
|
Nervous system disorders
Sensory neuropathy
|
5.9%
2/34
|
18.8%
6/32
|
|
Cardiac disorders
Sinus arrythmia
|
2.9%
1/34
|
3.1%
1/32
|
|
Infections and infestations
Skin (cellulitis)
|
0.00%
0/34
|
3.1%
1/32
|
|
Skin and subcutaneous tissue disorders
Skin bruising
|
2.9%
1/34
|
3.1%
1/32
|
|
General disorders
Sweating
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Taste alteration
|
2.9%
1/34
|
3.1%
1/32
|
|
Vascular disorders
Thrombosis/embolism
|
0.00%
0/34
|
3.1%
1/32
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare
|
11.8%
4/34
|
12.5%
4/32
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare - infiltrating tumor in the orbit
|
0.00%
0/34
|
3.1%
1/32
|
|
Renal and urinary disorders
Ureter pain
|
2.9%
1/34
|
6.2%
2/32
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
14.7%
5/34
|
3.1%
1/32
|
|
Renal and urinary disorders
Urinary retention
|
2.9%
1/34
|
0.00%
0/32
|
|
Reproductive system and breast disorders
Vaginal bleeding
|
20.6%
7/34
|
18.8%
6/32
|
|
Reproductive system and breast disorders
Vaginal discharge
|
20.6%
7/34
|
21.9%
7/32
|
|
Reproductive system and breast disorders
Vaginal dryness
|
5.9%
2/34
|
0.00%
0/32
|
|
Respiratory, thoracic and mediastinal disorders
Voice change
|
2.9%
1/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Vomiting
|
17.6%
6/34
|
31.2%
10/32
|
|
Investigations
Weight gain
|
20.6%
7/34
|
12.5%
4/32
|
|
Investigations
Weight loss
|
2.9%
1/34
|
0.00%
0/32
|
Additional Information
Dr. Matthew Ellis
Washington University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place