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S1222 Trial (Everolimus, Anastrozole and Fulvestrant) in Post-Menopausal Stage IV Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02137837
Recruitment Status : Terminated (lack of accrual)
First Posted : May 14, 2014
Results First Posted : January 28, 2021
Last Update Posted : January 28, 2021
Sponsor:
Collaborators:
AstraZeneca
Novartis
Information provided by (Responsible Party):
Southwest Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Fulvestrant
Drug: Anastrozole
Drug: Everolimus
Drug: Placebo - Anastrozole
Drug: Placebo - Everolimus
Enrollment 37
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Anastrozole

Everolimus

Period Title: Overall Study
Started 13 12 12
Received Protocol Therapy 13 11 12
Completed 0 0 0
Not Completed 13 12 12
Reason Not Completed
Adverse Event             0             2             1
Refusal unrelated to adverse event             2             2             1
Progression/relapse             9             7             7
Not protocol specified             2             1             3
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole Total
Hide Arm/Group Description

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Anastrozole

Everolimus

Total of all reporting groups
Overall Number of Baseline Participants 13 12 12 37
Hide Baseline Analysis Population Description
Eligible participants randomized to study arms
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants 12 participants 12 participants 37 participants
63.4
(54.9 to 74.0)
62.6
(45.6 to 87.9)
60.5
(48.2 to 69.5)
62.0
(45.6 to 87.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 12 participants 37 participants
Female
13
 100.0%
12
 100.0%
12
 100.0%
37
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 12 participants 37 participants
Hispanic or Latino
1
   7.7%
2
  16.7%
0
   0.0%
3
   8.1%
Not Hispanic or Latino
12
  92.3%
10
  83.3%
12
 100.0%
34
  91.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 12 participants 37 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   8.3%
0
   0.0%
1
   2.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  15.4%
0
   0.0%
3
  25.0%
5
  13.5%
White
9
  69.2%
10
  83.3%
9
  75.0%
28
  75.7%
More than one race
1
   7.7%
0
   0.0%
0
   0.0%
1
   2.7%
Unknown or Not Reported
1
   7.7%
1
   8.3%
0
   0.0%
2
   5.4%
Disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 12 participants 37 participants
Measurable 9 10 9 28
Evaluable non-measurable disease 4 2 3 9
Prior Hormone  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 12 participants 37 participants
Prior adjuvant hormonal therapy completed >5 years ago
3
  23.1%
1
   8.3%
2
  16.7%
6
  16.2%
Prior adjuvant hormonal therapy completed 1-5 years ago
4
  30.8%
5
  41.7%
6
  50.0%
15
  40.5%
De novo presentation of metastatic disease or no prior adjuvant hormonal therapy
6
  46.2%
6
  50.0%
4
  33.3%
16
  43.2%
1.Primary Outcome
Title Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus )
Hide Description From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive are censored at date of last contact.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants randomized to study arms. This includes 1 participant on arm 2 who did not receive protocol treatment and is assumed to be a non-responder for response assessment.
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Overall Number of Participants Analyzed 13 12
Median (95% Confidence Interval)
Unit of Measure: months
14.0 [1] 
(NA to NA)
11.3 [1] 
(NA to NA)
[1]
Confidence intervals not calculated due to small sample size
2.Primary Outcome
Title Progression-free Survival (Fulvestrant Versus Fulvestrant + Everolimus + Anastrozole)
Hide Description From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants who were randomized to study arms and received protocol therapy
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 13 12
Median (95% Confidence Interval)
Unit of Measure: months
14.0 [1] 
(NA to NA)
9.9 [1] 
(NA to NA)
[1]
Confidence intervals not calculated due to small sample size
3.Secondary Outcome
Title Progression Free Survival (Fulvestrant + Everolimus vs Fulvestrant + Everolimus + Anastrozole)
Hide Description From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants randomized to study arms. This includes 1 participant on arm 2 who did not receive protocol treatment and is assumed to be a non-responder for response assessment.
Arm/Group Title Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 12 12
Median (95% Confidence Interval)
Unit of Measure: months
11.3 [1] 
(NA to NA)
9.90 [1] 
(NA to NA)
[1]
Confidence intervals not calculated due to small sample size
4.Secondary Outcome
Title Overall Survival
Hide Description From date of registration to date of death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants randomized to study arms. This includes 1 participant on arm 2 who did not receive protocol treatment and is assumed to be a non-responder for response assessment.
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 13 12 12
Median (95% Confidence Interval)
Unit of Measure: months
46.8 [1] 
(NA to NA)
56.6 [1] 
(NA to NA)
33.6 [1] 
(NA to NA)
[1]
Confidence intervals not calculated due to small sample size
5.Secondary Outcome
Title Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Hide Description Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame Duration of treatment and follow up until death or 5 years post registration
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants who received at least one dose of protocol treatment.
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 & 15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 & 15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 & 15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 13 11 12
Measure Type: Number
Unit of Measure: Participants
Abdominal pain 0 1 0
Anorexia 0 1 1
Aspartate aminotransferase increased 0 1 0
Dehydration 0 2 1
Diarrhea 0 1 0
Fatigue 0 2 0
Flu like symptoms 0 1 0
Generalized muscle weakness 0 1 0
Hyperglycemia 0 1 0
Hypertension 0 2 2
Hypocalcemia 0 1 0
Hypokalemia 0 2 1
Hyponatremia 0 1 0
Hypophosphatemia 0 1 0
Hypotension 0 0 1
Localized edema 0 1 0
Lymphocyte count decreased 0 1 0
Mucositis oral 0 0 1
Neutrophil count decreased 0 2 0
Rash maculo-papular 0 0 1
Resp, thoracic and mediastinal disorders - Other 0 1 0
Sore throat 0 0 1
Thromboembolic event 0 0 1
Vomiting 0 1 0
White blood cell decreased 0 1 0
6.Secondary Outcome
Title Response Rate
Hide Description Proportion of participants who have confirmed or unconfirmed partial or complete response to therapy
Time Frame assessed every 12 weeks, up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants with measurable disease.
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 9 10 9
Measure Type: Number
Unit of Measure: percentage of participants
22 60 44
7.Secondary Outcome
Title Clinical Benefit Rate
Hide Description Proportion of participants who have confirmed and unconfirmed partial response, complete response or stable disease.
Time Frame assessed every 12 weeks, up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants randomized to study arms. This includes 1 participant on arm 2 who did not receive protocol treatment and is assumed to be a non-responder for response assessment.
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 13 12 12
Measure Type: Number
Unit of Measure: percentage of participants
69 83 67
8.Secondary Outcome
Title Molecular Determinants of Response in Circulating Tumor Cells: CTC-ETI
Hide Description CTC-Endocrine Therapy Index (CTC-ETI) on the CellSearch® platform. Based on enumeration of CTC/7.5 mL of whole blood, with >= 5 being elevated. (Due to limited samples collected, full analysis was not able to be performed as planned, so outcome measure reported here is number with elevated Day 1 CTC.)
Time Frame Day 1, Day 29, time of progression (Day 29 to be collected only if Day 1 CTC was elevated.)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with Day 1 whole blood specimen submitted.
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description:

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant without continuing placebos.)

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus without continuing placebos.)

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. (Note: after study unblinding at time of permanent study closure, participants on this arm received fulvestrant and unblinded everolimus and anastrozole.)

Fulvestrant

Anastrozole

Everolimus

Overall Number of Participants Analyzed 5 5 3
Measure Type: Count of Participants
Unit of Measure: Participants
1
  20.0%
1
  20.0%
0
   0.0%
Time Frame Duration of treatment and follow up until death or 5 years post registration
Adverse Event Reporting Description 36 participants who were eligible and received protocol therapy were assessed for AEs.
 
Arm/Group Title Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Hide Arm/Group Description

Participants receive an injection of fulvestrant in each buttock on Days 1 & 15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Placebo - Anastrozole

Placebo - Everolimus

Participants receive an injection of fulvestrant in each buttock on Days 1 & 15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Everolimus

Placebo - Anastrozole

Participants receive an injection of fulvestrant in each buttock on Days 1 & 15 for Cycle 1 and then Day 1 only for subsequent cycles. Participants also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.

Fulvestrant

Anastrozole

Everolimus

All-Cause Mortality
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/13 (61.54%)   6/12 (50.00%)   6/12 (50.00%) 
Hide Serious Adverse Events
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/11 (0.00%)   0/12 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo Arm 3: Fulvestrant + Everolimus + Anastrozole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/13 (100.00%)   11/11 (100.00%)   12/12 (100.00%) 
Blood and lymphatic system disorders       
Anemia   4/13 (30.77%)  8/11 (72.73%)  6/12 (50.00%) 
Blood and lymphatic system disorders - Other   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Cardiac disorders       
Atrial fibrillation   1/13 (7.69%)  0/11 (0.00%)  1/12 (8.33%) 
Atrioventricular block first degree   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Cardiac disorders-Other   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Chest pain - cardiac   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Left ventricular systolic dysfunction   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Palpitations   1/13 (7.69%)  1/11 (9.09%)  0/12 (0.00%) 
Pericardial effusion   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Sinus tachycardia   1/13 (7.69%)  3/11 (27.27%)  0/12 (0.00%) 
Ear and labyrinth disorders       
Ear and labyrinth disorders-Other   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Ear pain   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
External ear inflammation   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Tinnitus   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Vertigo   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Eye disorders       
Blurred vision   0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Conjunctivitis   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Eye disorders-Other   2/13 (15.38%)  1/11 (9.09%)  0/12 (0.00%) 
Floaters   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Watering eyes   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Gastrointestinal disorders       
Abdominal pain   3/13 (23.08%)  4/11 (36.36%)  1/12 (8.33%) 
Anal hemorrhage   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Ascites   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Bloating   0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Colitis   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Constipation   4/13 (30.77%)  6/11 (54.55%)  7/12 (58.33%) 
Dental caries   1/13 (7.69%)  0/11 (0.00%)  1/12 (8.33%) 
Diarrhea   2/13 (15.38%)  5/11 (45.45%)  4/12 (33.33%) 
Dry mouth   3/13 (23.08%)  3/11 (27.27%)  0/12 (0.00%) 
Dyspepsia   0/13 (0.00%)  4/11 (36.36%)  3/12 (25.00%) 
Dysphagia   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Esophagitis   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Fecal incontinence   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Flatulence   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Gastroesophageal reflux disease   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Gastrointestinal disorders-Other   1/13 (7.69%)  2/11 (18.18%)  0/12 (0.00%) 
Gastrointestinal pain   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Ileus   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Mucositis oral   3/13 (23.08%)  7/11 (63.64%)  8/12 (66.67%) 
Nausea   5/13 (38.46%)  6/11 (54.55%)  4/12 (33.33%) 
Oral pain   2/13 (15.38%)  2/11 (18.18%)  3/12 (25.00%) 
Rectal hemorrhage   1/13 (7.69%)  1/11 (9.09%)  0/12 (0.00%) 
Stomach pain   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Vomiting   1/13 (7.69%)  3/11 (27.27%)  4/12 (33.33%) 
General disorders       
Chills   1/13 (7.69%)  2/11 (18.18%)  1/12 (8.33%) 
Edema face   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Edema limbs   4/13 (30.77%)  6/11 (54.55%)  3/12 (25.00%) 
Fatigue   10/13 (76.92%)  10/11 (90.91%)  7/12 (58.33%) 
Fever   3/13 (23.08%)  3/11 (27.27%)  1/12 (8.33%) 
Flu like symptoms   0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
General disorders and admin site conditions - Other   1/13 (7.69%)  3/11 (27.27%)  0/12 (0.00%) 
Injection site reaction   2/13 (15.38%)  1/11 (9.09%)  0/12 (0.00%) 
Localized edema   0/13 (0.00%)  3/11 (27.27%)  1/12 (8.33%) 
Malaise   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Non-cardiac chest pain   0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%) 
Pain   4/13 (30.77%)  2/11 (18.18%)  3/12 (25.00%) 
Immune system disorders       
Allergic reaction   1/13 (7.69%)  1/11 (9.09%)  0/12 (0.00%) 
Immune system disorders-Other   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Infections and infestations       
Infections and infestations-Other   1/13 (7.69%)  4/11 (36.36%)  2/12 (16.67%) 
Mucosal infection   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Rhinitis infective   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Sinusitis   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Skin infection   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Tooth infection   1/13 (7.69%)  0/11 (0.00%)  1/12 (8.33%) 
Upper respiratory infection   2/13 (15.38%)  1/11 (9.09%)  3/12 (25.00%) 
Urinary tract infection   0/13 (0.00%)  0/11 (0.00%)  2/12 (16.67%) 
Vaginal infection   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Injury, poisoning and procedural complications       
Burn   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Dermatitis radiation   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Fracture   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Investigations       
Alanine aminotransferase increased   2/13 (15.38%)  6/11 (54.55%)  3/12 (25.00%) 
Alkaline phosphatase increased   3/13 (23.08%)  2/11 (18.18%)  1/12 (8.33%) 
Aspartate aminotransferase increased   4/13 (30.77%)  7/11 (63.64%)  4/12 (33.33%) 
Blood bilirubin increased   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Cholesterol high   4/13 (30.77%)  10/11 (90.91%)  5/12 (41.67%) 
Creatinine increased   0/13 (0.00%)  1/11 (9.09%)  2/12 (16.67%) 
Electrocardiogram QT corrected interval prolonged   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
INR increased   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Investigations-Other   0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%) 
Lipase increased   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Lymphocyte count decreased   1/13 (7.69%)  7/11 (63.64%)  4/12 (33.33%) 
Neutrophil count decreased   0/13 (0.00%)  3/11 (27.27%)  1/12 (8.33%) 
Platelet count decreased   1/13 (7.69%)  4/11 (36.36%)  4/12 (33.33%) 
Weight gain   1/13 (7.69%)  1/11 (9.09%)  2/12 (16.67%) 
Weight loss   2/13 (15.38%)  6/11 (54.55%)  3/12 (25.00%) 
White blood cell decreased   0/13 (0.00%)  7/11 (63.64%)  4/12 (33.33%) 
Metabolism and nutrition disorders       
Anorexia   3/13 (23.08%)  7/11 (63.64%)  3/12 (25.00%) 
Dehydration   0/13 (0.00%)  3/11 (27.27%)  1/12 (8.33%) 
Glucose intolerance   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hypercalcemia   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Hyperglycemia   8/13 (61.54%)  7/11 (63.64%)  5/12 (41.67%) 
Hypernatremia   0/13 (0.00%)  2/11 (18.18%)  3/12 (25.00%) 
Hypertriglyceridemia   4/13 (30.77%)  8/11 (72.73%)  6/12 (50.00%) 
Hypoalbuminemia   1/13 (7.69%)  7/11 (63.64%)  1/12 (8.33%) 
Hypocalcemia   2/13 (15.38%)  2/11 (18.18%)  2/12 (16.67%) 
Hypokalemia   2/13 (15.38%)  5/11 (45.45%)  3/12 (25.00%) 
Hypomagnesemia   0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Hyponatremia   2/13 (15.38%)  4/11 (36.36%)  2/12 (16.67%) 
Hypophosphatemia   1/13 (7.69%)  1/11 (9.09%)  1/12 (8.33%) 
Metabolism and nutrition disorders - Other, specify   0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%) 
Musculoskeletal and connective tissue disorders       
Arthralgia   1/13 (7.69%)  3/11 (27.27%)  4/12 (33.33%) 
Arthritis   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Avascular necrosis   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Back pain   3/13 (23.08%)  2/11 (18.18%)  1/12 (8.33%) 
Bone pain   5/13 (38.46%)  2/11 (18.18%)  3/12 (25.00%) 
Chest wall pain   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Generalized muscle weakness   1/13 (7.69%)  2/11 (18.18%)  0/12 (0.00%) 
Joint range of motion decreased   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Musculoskeletal and connective tiss disorder - Other   1/13 (7.69%)  3/11 (27.27%)  0/12 (0.00%) 
Myalgia   4/13 (30.77%)  1/11 (9.09%)  2/12 (16.67%) 
Neck pain   1/13 (7.69%)  1/11 (9.09%)  0/12 (0.00%) 
Osteonecrosis of jaw   1/13 (7.69%)  0/11 (0.00%)  1/12 (8.33%) 
Pain in extremity   5/13 (38.46%)  5/11 (45.45%)  1/12 (8.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor pain   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Nervous system disorders       
Dizziness   0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%) 
Dysesthesia   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Dysgeusia   1/13 (7.69%)  6/11 (54.55%)  0/12 (0.00%) 
Headache   4/13 (30.77%)  4/11 (36.36%)  5/12 (41.67%) 
Memory impairment   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Nervous system disorders-Other   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Paresthesia   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Peripheral motor neuropathy   0/13 (0.00%)  2/11 (18.18%)  2/12 (16.67%) 
Peripheral sensory neuropathy   3/13 (23.08%)  5/11 (45.45%)  1/12 (8.33%) 
Syncope   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Psychiatric disorders       
Agitation   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Anxiety   1/13 (7.69%)  2/11 (18.18%)  1/12 (8.33%) 
Depression   2/13 (15.38%)  0/11 (0.00%)  1/12 (8.33%) 
Insomnia   3/13 (23.08%)  3/11 (27.27%)  2/12 (16.67%) 
Restlessness   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Renal and urinary disorders       
Acute kidney injury   0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Chronic kidney disease   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Cystitis noninfective   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hematuria   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Renal and urinary disorders-Other   1/13 (7.69%)  1/11 (9.09%)  0/12 (0.00%) 
Urinary frequency   1/13 (7.69%)  1/11 (9.09%)  2/12 (16.67%) 
Urinary incontinence   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Urinary tract pain   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Urinary urgency   0/13 (0.00%)  1/11 (9.09%)  2/12 (16.67%) 
Reproductive system and breast disorders       
Reproductive system and breast disorders - Other   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Vaginal discharge   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Vaginal pain   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis   2/13 (15.38%)  1/11 (9.09%)  0/12 (0.00%) 
Atelectasis   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Cough   5/13 (38.46%)  7/11 (63.64%)  4/12 (33.33%) 
Dyspnea   6/13 (46.15%)  3/11 (27.27%)  3/12 (25.00%) 
Epistaxis   0/13 (0.00%)  1/11 (9.09%)  2/12 (16.67%) 
Hoarseness   2/13 (15.38%)  0/11 (0.00%)  1/12 (8.33%) 
Nasal congestion   0/13 (0.00%)  1/11 (9.09%)  2/12 (16.67%) 
Pleural effusion   2/13 (15.38%)  0/11 (0.00%)  0/12 (0.00%) 
Pneumonitis   0/13 (0.00%)  3/11 (27.27%)  1/12 (8.33%) 
Postnasal drip   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Productive cough   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Resp, thoracic and mediastinal disorders - Other   0/13 (0.00%)  3/11 (27.27%)  1/12 (8.33%) 
Sleep apnea   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Sore throat   3/13 (23.08%)  3/11 (27.27%)  2/12 (16.67%) 
Voice alteration   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Wheezing   1/13 (7.69%)  1/11 (9.09%)  2/12 (16.67%) 
Skin and subcutaneous tissue disorders       
Alopecia   1/13 (7.69%)  1/11 (9.09%)  1/12 (8.33%) 
Dry skin   1/13 (7.69%)  3/11 (27.27%)  1/12 (8.33%) 
Erythema multiforme   0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Nail discoloration   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Pruritus   0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%) 
Rash acneiform   1/13 (7.69%)  4/11 (36.36%)  1/12 (8.33%) 
Rash maculo-papular   0/13 (0.00%)  4/11 (36.36%)  3/12 (25.00%) 
Skin and subcutaneous tissue disorders - Other   2/13 (15.38%)  2/11 (18.18%)  0/12 (0.00%) 
Skin hyperpigmentation   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Skin induration   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Skin ulceration   1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%) 
Vascular disorders       
Flushing   0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hot flashes   6/13 (46.15%)  6/11 (54.55%)  5/12 (41.67%) 
Hypertension   2/13 (15.38%)  5/11 (45.45%)  4/12 (33.33%) 
Hypotension   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Thromboembolic event   0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Vascular disorders-Other   0/13 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Breast Committee Statistician
Organization: SWOG Statistics and Data Management Center
Phone: 2066674623
EMail: dlew@fredhutch.org
Layout table for additonal information
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02137837    
Other Study ID Numbers: S1222
First Submitted: May 12, 2014
First Posted: May 14, 2014
Results First Submitted: January 5, 2021
Results First Posted: January 28, 2021
Last Update Posted: January 28, 2021