Trial Outcomes & Findings for Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure (NCT NCT00570921)
NCT ID: NCT00570921
Last Updated: 2017-02-23
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
Duration of time start of treatment to time of documented progression or death
Results posted on
2017-02-23
Participant Flow
Patients were recruited at a single location, University of Kentucky Markey Cancer Center, between March 2008 and October 2012.
Participant milestones
| Measure |
Fulvestrant + Everolimus
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Overall Study
STARTED
|
33
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Fulvestrant + Everolimus
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure
Baseline characteristics by cohort
| Measure |
Fulvestrant & Everolimus
n=31 Participants
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
Everolimus: Everolimus tablets, two-5 mg tablets a day
Fulvestrant: intramuscular, 500 mg in two divided doses- one on each side- on day 1, then 250mg on day 14, then 250 mg on day 28 and every 4 weeks +/- 3 days thereafter
|
|---|---|
|
Age, Continuous
|
54 years
n=99 Participants
|
|
Gender
Female
|
31 Participants
n=99 Participants
|
|
Gender
Male
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
27 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=99 Participants
|
|
Hormone Receptor Status
ER-positive/progesterone receptor (PgR)-positive
|
26 participants
n=99 Participants
|
|
Hormone Receptor Status
ER-positive/progesterone receptor (PgR)-negative
|
5 participants
n=99 Participants
|
|
Human epidermal growth factor receptor 2 (HER2) Status
Negative
|
29 participants
n=99 Participants
|
|
Human epidermal growth factor receptor 2 (HER2) Status
Positive
|
2 participants
n=99 Participants
|
|
Histology
Ductal
|
26 participants
n=99 Participants
|
|
Histology
Lobular
|
3 participants
n=99 Participants
|
|
Histology
Mixed ductal and lobular
|
1 participants
n=99 Participants
|
|
Histology
Intracystic papillary
|
1 participants
n=99 Participants
|
|
Relapsed versus de novo metastasis
Relapse
|
24 participants
n=99 Participants
|
|
Relapsed versus de novo metastasis
De novo
|
7 participants
n=99 Participants
|
|
Number of metastatic sites
1
|
4 participants
n=99 Participants
|
|
Number of metastatic sites
2
|
10 participants
n=99 Participants
|
|
Number of metastatic sites
3 or more
|
17 participants
n=99 Participants
|
|
Bone Disease
Yes
|
20 participants
n=99 Participants
|
|
Bone Disease
No
|
11 participants
n=99 Participants
|
|
Liver Disease
Yes
|
19 participants
n=99 Participants
|
|
Liver Disease
No
|
12 participants
n=99 Participants
|
|
Lung Disease
Yes
|
17 participants
n=99 Participants
|
|
Lung Disease
No
|
14 participants
n=99 Participants
|
|
Intact Primary Tumor
Yes
|
6 participants
n=99 Participants
|
|
Intact Primary Tumor
No
|
25 participants
n=99 Participants
|
|
Skin Disease
Yes
|
4 participants
n=99 Participants
|
|
Skin Disease
No
|
27 participants
n=99 Participants
|
|
Prior aromatase inhibitor (AI) therapy within 6 months of enrollment
|
31 participants
n=99 Participants
|
|
Prior tamoxifen therapy
Yes
|
25 participants
n=99 Participants
|
|
Prior tamoxifen therapy
No
|
6 participants
n=99 Participants
|
|
Prior Chemotherapy
Yes
|
22 participants
n=99 Participants
|
|
Prior Chemotherapy
No
|
9 participants
n=99 Participants
|
|
3 or more prior endocrine therapies
Yes
|
8 participants
n=99 Participants
|
|
3 or more prior endocrine therapies
No
|
23 participants
n=99 Participants
|
|
Two prior aromatase inhibitor therapy
Yes
|
7 participants
n=99 Participants
|
|
Two prior aromatase inhibitor therapy
No
|
24 participants
n=99 Participants
|
|
AI Sensitivity
Sensitive
|
21 participants
n=99 Participants
|
|
AI Sensitivity
Resistant
|
10 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Duration of time start of treatment to time of documented progression or deathOutcome measures
| Measure |
Fulvestrant + Everolimus
n=31 Participants
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Time to Progression
|
7.4 months
Interval 1.9 to 12.1
|
SECONDARY outcome
Timeframe: Evaluated 60 days after therapy startPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Fulvestrant + Everolimus
n=31 Participants
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Objective Response Rates
|
4 participants
|
SECONDARY outcome
Timeframe: Duration of response or stable disease for 24 weeks or moreClinical benefit rate is defined as a complete response, partial response, or stable disease (CR, PR, SD) by Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for a minimum of at least 24 weeks or more.
Outcome measures
| Measure |
Fulvestrant + Everolimus
n=31 Participants
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Clinical Benefit Rate
|
15 participants
|
Adverse Events
Fulvestrant + Everolimus
Serious events: 5 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fulvestrant + Everolimus
n=33 participants at risk
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Cardiac disorders
Left Ventricular Thrombus
|
3.0%
1/33
|
|
Hepatobiliary disorders
Acute Cholecystitis
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
3.0%
1/33
|
|
Gastrointestinal disorders
Nausea
|
3.0%
1/33
|
|
Renal and urinary disorders
Renal Failure
|
3.0%
1/33
|
Other adverse events
| Measure |
Fulvestrant + Everolimus
n=33 participants at risk
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
|
|---|---|
|
Investigations
AST Elevation
|
81.8%
27/33
|
|
Investigations
ALT Elevation
|
72.7%
24/33
|
|
Blood and lymphatic system disorders
Anemia
|
69.7%
23/33
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
66.7%
22/33
|
|
Investigations
Hypercholesterolemia
|
63.6%
21/33
|
|
Metabolism and nutrition disorders
Hypokalemia
|
57.6%
19/33
|
|
Respiratory, thoracic and mediastinal disorders
Mucositis
|
54.5%
18/33
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
51.5%
17/33
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
51.5%
17/33
|
|
Investigations
Weight loss
|
45.5%
15/33
|
|
Blood and lymphatic system disorders
Leukopenia
|
42.4%
14/33
|
|
Skin and subcutaneous tissue disorders
Rash/skin changes
|
39.4%
13/33
|
|
Gastrointestinal disorders
Nausea
|
30.3%
10/33
|
|
General disorders
Fatigue
|
30.3%
10/33
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
18.2%
6/33
|
|
Gastrointestinal disorders
Vomiting
|
18.2%
6/33
|
|
Metabolism and nutrition disorders
Anorexia
|
18.2%
6/33
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
18.2%
6/33
|
|
General disorders
Edema
|
18.2%
6/33
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
18.2%
6/33
|
|
Metabolism and nutrition disorders
Hyponatremia
|
18.2%
6/33
|
|
Gastrointestinal disorders
Constipation
|
15.2%
5/33
|
|
Gastrointestinal disorders
Diarrhea
|
15.2%
5/33
|
|
Skin and subcutaneous tissue disorders
Itching/dry skin only
|
9.1%
3/33
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place