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Trial record 1 of 1 for:    PrECOG 0102
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Study of Fulvestrant +/- Everolimus in Post-Menopausal, Hormone-Receptor + Metastatic Breast Ca Resistant to AI (PrE0102)

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ClinicalTrials.gov Identifier: NCT01797120
Recruitment Status : Completed
First Posted : February 22, 2013
Results First Posted : April 30, 2018
Last Update Posted : May 30, 2018
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
PrECOG, LLC.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Drug: Fulvestrant
Drug: Everolimus
Drug: Placebo
Enrollment 131
Recruitment Details A total of 131 patients were enrolled from 23 institutions between May 2013 and November 2015.
Pre-assignment Details  
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo
Hide Arm/Group Description

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Period Title: Overall Study
Started 66 65
Completed 0 0
Not Completed 66 65
Reason Not Completed
Disesae progression             37             49
Adverse Event             13             5
Withdrawal by Subject             6             6
Symptomatic progression             2             1
Non-compliance             1             0
Physician Decision             3             0
still on treatment             2             4
never start protocol therapy             2             0
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo Total
Hide Arm/Group Description

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Total of all reporting groups
Overall Number of Baseline Participants 66 65 131
Hide Baseline Analysis Population Description
all randomized patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 66 participants 65 participants 131 participants
64
(39 to 92)
59
(35 to 85)
63
(35 to 92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 65 participants 131 participants
Female
66
 100.0%
65
 100.0%
131
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 65 participants 131 participants
White
56
  84.8%
49
  75.4%
105
  80.2%
Black
8
  12.1%
11
  16.9%
19
  14.5%
Others
2
   3.0%
5
   7.7%
7
   5.3%
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival documented by Physical Exam, CT Scan or MRI in post-menopausal patients with hormone-receptor positive metastatic breast cancer that is resistant to aromatase inhibitor therapy treated with fulvestrant and everolimus compared to fulvestrant alone from randomization to documented disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Every 3 months until progression or up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
all randomized patients
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo
Hide Arm/Group Description:

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Overall Number of Participants Analyzed 66 65
Median (95% Confidence Interval)
Unit of Measure: months
10.3
(7.6 to 13.8)
5.1
(3.0 to 8.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fulvestrant & Everolimus, Fulvestrant & Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Log Rank
Comments Log rank test was stratified on ECOG performance status, measurable disease, and prior chemotherapy for metastatic disease
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.40 to 0.92
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Clinical Benefit Rate
Hide Description Clinical benefit rate is defined as number of patients with objective response (complete response or partial response) or stable disease for at least 24 weeks divided by number of patients randomized in each arm. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease; Complete Response (CR) is defined as disappearance of all target lesions.
Time Frame Every 3 months until progression or up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
all randomized patients
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo
Hide Arm/Group Description:

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Overall Number of Participants Analyzed 66 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of patients
0.636
(0.509 to 0.751)
0.415
(0.294 to 0.544)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fulvestrant & Everolimus, Fulvestrant & Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate
Hide Description Objective response rate is defined as number of patients with complete or partial response (by Physical Exam, CT or MRI) divided by number of patients randomized in each arm
Time Frame Every 3 months until progression or up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
all randomized patients
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo
Hide Arm/Group Description:

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Overall Number of Participants Analyzed 66 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of patients
0.182
(0.098 to 0.296)
0.123
(0.055 to 0.228)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fulvestrant & Everolimus, Fulvestrant & Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival will be characterized using Kaplan-Meier plots and other descriptive metrics.
Time Frame Every 3 months until progression or up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
all randomized patients
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo
Hide Arm/Group Description:

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Overall Number of Participants Analyzed 66 65
Median (95% Confidence Interval)
Unit of Measure: months
28.3
(19.5 to 29.6)
31.4 [1] 
(21.8 to NA)
[1]
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment
Time Frame Assessed at the end of each cycle (1 cycle=4 weeks) while on treatment and 30 days after the last dose of protocol therapy. Treatment continued for a maximum of 48 weeks (12 cycles) in the absence of disease progression, unacceptable toxicity or withdrawal of consent.
Adverse Event Reporting Description All-cause mortality is the death rate among all patients, rather than in patients who received at least one dose of protocol therapy and reported toxicity data.
 
Arm/Group Title Fulvestrant & Everolimus Fulvestrant & Placebo
Hide Arm/Group Description

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Everolimus: Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.

Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

All-Cause Mortality
Fulvestrant & Everolimus Fulvestrant & Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   30/66 (45.45%)   21/65 (32.31%) 
Show Serious Adverse Events Hide Serious Adverse Events
Fulvestrant & Everolimus Fulvestrant & Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   31/64 (48.44%)   5/65 (7.69%) 
Blood and lymphatic system disorders     
Anemia  1  2/64 (3.13%)  1/65 (1.54%) 
Lymphocytopenia  1  2/64 (3.13%)  0/65 (0.00%) 
Hypertension  1  2/64 (3.13%)  0/65 (0.00%) 
Neutropenia  1  2/64 (3.13%)  0/65 (0.00%) 
Thrombocytopenia  1  1/64 (1.56%)  0/65 (0.00%) 
Cardiac disorders     
Thromboembolic Event  1  1/64 (1.56%)  0/65 (0.00%) 
Gastrointestinal disorders     
Oral mucositis  1  7/64 (10.94%)  0/65 (0.00%) 
Diarrhea  1  2/64 (3.13%)  1/65 (1.54%) 
General disorders     
Fatigue  1  4/64 (6.25%)  3/65 (4.62%) 
Hepatobiliary disorders     
Elevated AST  1  2/64 (3.13%)  1/65 (1.54%) 
Elevated ALT  1  1/64 (1.56%)  0/65 (0.00%) 
Infections and infestations     
Esophageal Candidiasis  1  1/64 (1.56%)  0/65 (0.00%) 
Esophagitis  1  1/64 (1.56%)  0/65 (0.00%) 
Laryngeal Inflammation  1  1/64 (1.56%)  0/65 (0.00%) 
Urinary Tract Infection  1  1/64 (1.56%)  0/65 (0.00%) 
Metabolism and nutrition disorders     
Hypertriglyceridemia  1  1/64 (1.56%)  0/65 (0.00%) 
Hyperglycemia  1  2/64 (3.13%)  0/65 (0.00%) 
Hyponatremia  1  2/64 (3.13%)  0/65 (0.00%) 
Hypokalemia  1  1/64 (1.56%)  0/65 (0.00%) 
Hypophosphatemia  1  1/64 (1.56%)  0/65 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  2/64 (3.13%)  0/65 (0.00%) 
Pneumonitis  1  4/64 (6.25%)  0/65 (0.00%) 
Hypoxia  1  1/64 (1.56%)  0/65 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/64 (1.56%)  0/65 (0.00%) 
Pruritus  1  1/64 (1.56%)  0/65 (0.00%) 
Surgical and medical procedures     
Surgical and Medical Procedures  1  1/64 (1.56%)  0/65 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fulvestrant & Everolimus Fulvestrant & Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   59/64 (92.19%)   38/65 (58.46%) 
Blood and lymphatic system disorders     
Anemia  1  18/64 (28.13%)  3/65 (4.62%) 
Neutropenia  1  5/64 (7.81%)  2/65 (3.08%) 
Thrombocytopenia  1  5/64 (7.81%)  0/65 (0.00%) 
White blood cell decreased  1  4/64 (6.25%)  1/65 (1.54%) 
Cardiac disorders     
Hot flashes  1  5/64 (7.81%)  4/65 (6.15%) 
Gastrointestinal disorders     
Oral mucositis  1  26/64 (40.63%)  8/65 (12.31%) 
Anorexia  1  22/64 (34.38%)  4/65 (6.15%) 
Nausea  1  16/64 (25.00%)  12/65 (18.46%) 
Diarrhea  1  13/64 (20.31%)  4/65 (6.15%) 
Dysgeusia  1  8/64 (12.50%)  6/65 (9.23%) 
Vomitting  1  7/64 (10.94%)  3/65 (4.62%) 
Dry mouth  1  4/64 (6.25%)  0/65 (0.00%) 
Insomnia  1  4/64 (6.25%)  0/65 (0.00%) 
General disorders     
Fatigue  1  23/64 (35.94%)  11/65 (16.92%) 
Weight loss  1  9/64 (14.06%)  3/65 (4.62%) 
Chills  1  7/64 (10.94%)  0/65 (0.00%) 
Headache  1  6/64 (9.38%)  6/65 (9.23%) 
Hepatobiliary disorders     
AST increased  1  4/64 (6.25%)  1/65 (1.54%) 
ALT increased  1  4/64 (6.25%)  1/65 (1.54%) 
Metabolism and nutrition disorders     
Hyperglycemia  1  10/64 (15.63%)  3/65 (4.62%) 
Hypertriglyceridemia  1  10/64 (15.63%)  2/65 (3.08%) 
Hypercholesterolemia  1  12/64 (18.75%)  2/65 (3.08%) 
Hypokalemia  1  4/64 (6.25%)  1/65 (1.54%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  15/64 (23.44%)  1/65 (1.54%) 
Dyspnea  1  8/64 (12.50%)  2/65 (3.08%) 
Epistaxis  1  8/64 (12.50%)  0/65 (0.00%) 
Pneumonitis  1  7/64 (10.94%)  0/65 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  23/64 (35.94%)  3/65 (4.62%) 
Dry skin  1  8/64 (12.50%)  0/65 (0.00%) 
Pruritus  1  12/64 (18.75%)  2/65 (3.08%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Name/Title: Carolyn Andrews
Organization: PrECOG, LLC
Phone: 267-207-4070
Responsible Party: PrECOG, LLC.
ClinicalTrials.gov Identifier: NCT01797120     History of Changes
Other Study ID Numbers: PrE0102
First Submitted: February 14, 2013
First Posted: February 22, 2013
Results First Submitted: March 5, 2018
Results First Posted: April 30, 2018
Last Update Posted: May 30, 2018