Trial Outcomes & Findings for A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1) (NCT NCT01919229)
NCT ID: NCT01919229
Last Updated: 2016-01-01
Results Overview
Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.
TERMINATED
PHASE2
14 participants
Day 1, Day15
2016-01-01
Participant Flow
20 patients were screened, of those 14 patients completed the Screening phase and were randomized. 6 patients discontinued during the Screening phase; 3 patients were considered screen failure and 3 patients discontinued due to patient's decision.
Participant milestones
| Measure |
Letrozole
Letrozole 2.5 mg alone once daily
|
LEE011 400mg + Letrozole
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
|
LEE011 600mg + Letrozole
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
6
|
4
|
|
Overall Study
COMPLETED
|
4
|
6
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Letrozole
Letrozole 2.5 mg alone once daily
|
LEE011 400mg + Letrozole
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
|
LEE011 600mg + Letrozole
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
|
|---|---|---|---|
|
Overall Study
Subject/guardian decision
|
0
|
0
|
1
|
Baseline Characteristics
A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)
Baseline characteristics by cohort
| Measure |
Letrozole
n=4 Participants
Letrozole 2.5 mg alone once daily
|
LEE011 400mg + Letrozole
n=6 Participants
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
|
LEE011 600mg + Letrozole
n=4 Participants
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.0 years
STANDARD_DEVIATION 5.48 • n=99 Participants
|
64.2 years
STANDARD_DEVIATION 9.91 • n=107 Participants
|
70.0 years
STANDARD_DEVIATION 4.24 • n=206 Participants
|
63.8 years
STANDARD_DEVIATION 8.66 • n=7 Participants
|
|
Age, Customized
< 65 years
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
|
Age, Customized
>=65 years
|
0 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
14 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Day 1, Day15Population: Since the study was terminated, no efficacy data was obtained.
Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 30 days after the last dosePopulation: Since the study was terminated, no efficacy data was obtained, but see Adverse Events (AE) section for all AEs collected.
Occurrence, frequency and severity of adverse events (AEs), laboratory abnormalities
Outcome measures
| Measure |
Letrozole
n=4 Participants
Letrozole 2.5 mg alone once daily
|
LEE011 400mg + Letrozole
n=6 Participants
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
|
LEE011 600mg + Letrozole
n=4 Participants
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
|
|---|---|---|---|
|
Safety and Tolerability of the Combination
Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of the Combination
Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of the Combination
Deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of the Combination
Other Adverse Events
|
2 Participants
|
5 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 14Population: Since the study was terminated, no efficacy data was obtained.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Since the study was terminated, no efficacy data was obtained.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 1, 8, 14 and 15Population: Since the study was terminated, no efficacy data was obtained.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 14Population: Since the study was terminated, no efficacy data was obtained.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 14Population: Since the study was terminated, no efficacy data was obtained.
Correlation between the QTc interval change from baseline and plasma concentrations of LEE011 and/or any relevant metabolites
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Since the study was terminated, no efficacy data was obtained.
Outcome measures
Outcome data not reported
Adverse Events
Letrozole2.5mgqd
LEE400mgqd+Letrozole2.5mgqd
LEE600mgqd+Letrozole2.5mgqd
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Letrozole2.5mgqd
n=4 participants at risk
Letrozole 2.5 mg alone once daily
|
LEE400mgqd+Letrozole2.5mgqd
n=6 participants at risk
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
|
LEE600mgqd+Letrozole2.5mgqd
n=4 participants at risk
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
|
|---|---|---|---|
|
Ear and labyrinth disorders
VERTIGO
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.00%
0/4
|
16.7%
1/6
|
0.00%
0/4
|
|
Gastrointestinal disorders
NAUSEA
|
25.0%
1/4
|
0.00%
0/6
|
75.0%
3/4
|
|
Gastrointestinal disorders
STOMATITIS
|
0.00%
0/4
|
16.7%
1/6
|
0.00%
0/4
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/4
|
0.00%
0/6
|
50.0%
2/4
|
|
General disorders
ASTHENIA
|
0.00%
0/4
|
33.3%
2/6
|
25.0%
1/4
|
|
General disorders
FATIGUE
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
General disorders
PYREXIA
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Immune system disorders
HYPERSENSITIVITY
|
0.00%
0/4
|
16.7%
1/6
|
0.00%
0/4
|
|
Infections and infestations
HERPES ZOSTER
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Infections and infestations
POST PROCEDURAL INFECTION
|
0.00%
0/4
|
16.7%
1/6
|
0.00%
0/4
|
|
Injury, poisoning and procedural complications
PROCEDURAL PAIN
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Injury, poisoning and procedural complications
SEROMA
|
0.00%
0/4
|
16.7%
1/6
|
0.00%
0/4
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
25.0%
1/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
25.0%
1/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Investigations
BLOOD CREATININE INCREASED
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Investigations
ELECTROCARDIOGRAM QT PROLONGED
|
0.00%
0/4
|
0.00%
0/6
|
50.0%
2/4
|
|
Investigations
LIPASE INCREASED
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
0.00%
0/4
|
0.00%
0/6
|
50.0%
2/4
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
25.0%
1/4
|
0.00%
0/6
|
0.00%
0/4
|
|
Reproductive system and breast disorders
BREAST PAIN
|
25.0%
1/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/4
|
16.7%
1/6
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
|
Vascular disorders
HOT FLUSH
|
0.00%
0/4
|
0.00%
0/6
|
25.0%
1/4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER