Trial Outcomes & Findings for Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score (NCT NCT02236572)
NCT ID: NCT02236572
Last Updated: 2022-02-01
Results Overview
(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
up to 26 weeks
Results posted on
2022-02-01
Participant Flow
Participant milestones
| Measure |
Aromatase Inhibitor Plus Everolimus
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Aromatase Inhibitor Plus Everolimus
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score
Baseline characteristics by cohort
| Measure |
Aromatase Inhibitor Plus Everolimus
n=17 Participants
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
Age, Continuous
|
66 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple or unknown
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
|
Clinical Tumor Size at Presentation - pt no.
T1
|
5 Participants
n=5 Participants
|
|
Clinical Tumor Size at Presentation - pt no.
T2
|
12 Participants
n=5 Participants
|
|
Clinical Tumor Size at Presentation - pt no.
T3
|
0 Participants
n=5 Participants
|
|
Nodal Status at Presentation
Positive (biopsy proven)
|
2 Participants
n=5 Participants
|
|
Nodal Status at Presentation
Negative
|
15 Participants
n=5 Participants
|
|
Tumor Histology
Ductal
|
12 Participants
n=5 Participants
|
|
Tumor Histology
Lobular
|
3 Participants
n=5 Participants
|
|
Tumor Histology
Unknown
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 26 weeksPopulation: 15 patients had surgery.
(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.
Outcome measures
| Measure |
Aromatase Inhibitor Plus Everolimus
n=15 Participants
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor
PEPI Score = 0
|
4 Participants
|
|
Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor
PEPI Score > 0
|
11 Participants
|
SECONDARY outcome
Timeframe: up to 26 weeksPopulation: Those that completed surgery
To obtain the PEPI score, risk points for relapse-free survival (RFS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).
Outcome measures
| Measure |
Aromatase Inhibitor Plus Everolimus
n=15 Participants
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
PEPI Score
|
3 units on a scale
Interval 0.0 to 7.0
|
SECONDARY outcome
Timeframe: Up to 26 weeksPopulation: All participants that were enrolled in the study.
Adverse events (using CTCAE (4.0)) that begin or worsen after informed consent were recorded. Adverse events are itemized in the adverse events module (in terms of total events and total participants experiencing events). Presented are the total number of participants that experience adverse events. For clarification, counts of participants that experienced serious adverse events and counts of participants that experienced 'other' (not serious) adverse events are presented separately.
Outcome measures
| Measure |
Aromatase Inhibitor Plus Everolimus
n=17 Participants
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
Participant Ability to Tolerate Study Treatment With Minimal Side Effects
Participants with Other (Not Including Serious) Adverse Events
|
17 Participants
|
|
Participant Ability to Tolerate Study Treatment With Minimal Side Effects
Participants with Serious Adverse Events
|
5 Participants
|
Adverse Events
Aromatase Inhibitor Plus Everolimus
Serious events: 5 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Aromatase Inhibitor Plus Everolimus
n=17 participants at risk
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
Cardiac disorders
Atrial Flutter
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
General disorders
Fever
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
Other adverse events
| Measure |
Aromatase Inhibitor Plus Everolimus
n=17 participants at risk
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
* Anastrozole 1 mg
* Letrozole 2.5 mg
* Exemestane 25 mg
|
|---|---|
|
General disorders
Fatigue
|
58.8%
10/17 • Number of events 16 • Up to 26 weeks
|
|
General disorders
Edema limbs
|
41.2%
7/17 • Number of events 8 • Up to 26 weeks
|
|
General disorders
Pain
|
35.3%
6/17 • Number of events 9 • Up to 26 weeks
|
|
General disorders
Edema face
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
General disorders
Fever
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
General disorders
Non-cardiac chest pain
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
General disorders
General disorders and administration site conditions - Other
|
5.9%
1/17 • Number of events 2 • Up to 26 weeks
|
|
General disorders
Malaise
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Gastrointestinal disorders
Mucositis oral
|
70.6%
12/17 • Number of events 22 • Up to 26 weeks
|
|
Gastrointestinal disorders
Nausea
|
35.3%
6/17 • Number of events 7 • Up to 26 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
29.4%
5/17 • Number of events 9 • Up to 26 weeks
|
|
Gastrointestinal disorders
Constipation
|
23.5%
4/17 • Number of events 4 • Up to 26 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Gastrointestinal disorders
Vomiting
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Gastrointestinal disorders
Flatulence
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Gastrointestinal disorders
Oral dysesthesia
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Gastrointestinal disorders
Oral pain
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Gastrointestinal disorders
Toothache
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
41.2%
7/17 • Number of events 10 • Up to 26 weeks
|
|
Investigations
Cholesterol high
|
41.2%
7/17 • Number of events 11 • Up to 26 weeks
|
|
Investigations
Alanine aminotransferase increased
|
35.3%
6/17 • Number of events 8 • Up to 26 weeks
|
|
Investigations
Platelet count decreased
|
17.6%
3/17 • Number of events 4 • Up to 26 weeks
|
|
Investigations
Weight loss
|
17.6%
3/17 • Number of events 5 • Up to 26 weeks
|
|
Investigations
Investigations - Other
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Investigations
Alkaline phosphatase increased
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Investigations
INR increased
|
5.9%
1/17 • Number of events 5 • Up to 26 weeks
|
|
Investigations
Neutrophil count decreased
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Investigations
White blood cell decreased
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
52.9%
9/17 • Number of events 20 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
29.4%
5/17 • Number of events 10 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
29.4%
5/17 • Number of events 5 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hypokalemia
|
29.4%
5/17 • Number of events 6 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
17.6%
3/17 • Number of events 4 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
17.6%
3/17 • Number of events 3 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
11.8%
2/17 • Number of events 3 • Up to 26 weeks
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
58.8%
10/17 • Number of events 13 • Up to 26 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
17.6%
3/17 • Number of events 3 • Up to 26 weeks
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
17.6%
3/17 • Number of events 3 • Up to 26 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.8%
2/17 • Number of events 3 • Up to 26 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Nervous system disorders
Dysgeusia
|
41.2%
7/17 • Number of events 7 • Up to 26 weeks
|
|
Nervous system disorders
Headache
|
35.3%
6/17 • Number of events 6 • Up to 26 weeks
|
|
Nervous system disorders
Dizziness
|
23.5%
4/17 • Number of events 4 • Up to 26 weeks
|
|
Nervous system disorders
Paresthesia
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
41.2%
7/17 • Number of events 12 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
35.3%
6/17 • Number of events 10 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
23.5%
4/17 • Number of events 9 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
17.6%
3/17 • Number of events 3 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.8%
2/17 • Number of events 3 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
52.9%
9/17 • Number of events 13 • Up to 26 weeks
|
|
Blood and lymphatic system disorders
Lymph node pain
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Vascular disorders
Hypertension
|
29.4%
5/17 • Number of events 26 • Up to 26 weeks
|
|
Vascular disorders
Hot flashes
|
23.5%
4/17 • Number of events 5 • Up to 26 weeks
|
|
Infections and infestations
Urinary tract infection
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Infections and infestations
Bronchial infection
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Infections and infestations
Mucosal infection
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Infections and infestations
Papulopustular rash
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Infections and infestations
Sinusitis
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Infections and infestations
Skin infection
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Psychiatric disorders
Insomnia
|
23.5%
4/17 • Number of events 4 • Up to 26 weeks
|
|
Psychiatric disorders
Anxiety
|
11.8%
2/17 • Number of events 2 • Up to 26 weeks
|
|
Psychiatric disorders
Depression
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Cardiac disorders
Atrial fibrillation
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Cardiac disorders
Atrial flutter
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Cardiac disorders
Cardiac disorders - Other
|
5.9%
1/17 • Number of events 2 • Up to 26 weeks
|
|
Ear and labyrinth disorders
Vertigo
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Ear and labyrinth disorders
Vestibular disorder
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Injury, poisoning and procedural complications
Bruising
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Injury, poisoning and procedural complications
Blurred vision
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Injury, poisoning and procedural complications
Eye disorders - Other
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Immune system disorders
Allergic reaction
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Renal and urinary disorders
Urinary frequency
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
5.9%
1/17 • Number of events 1 • Up to 26 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place