Trial Outcomes & Findings for Study of Efficacy of Ribociclib After Progression on CDK4/6 Inhibition in Patients With HR+ HER2- Advanced Breast Cancer (NCT NCT02632045)
NCT ID: NCT02632045
Last Updated: 2024-12-06
Results Overview
Progression free survival (PFS) is defined as the interval from the time of randomization until objective disease progression (local assessment) or death from any cause. Disease status will be assessed with comprehensive radiographic studies every three treatment cycles (approximately every 12 weeks (+/- 1 week)). Disease progression as assed by RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
169 participants
Primary outcome timeframe
Up to approximately 30 months
Results posted on
2024-12-06
Participant Flow
A total of 169 participants signed a consent form. Of those, 47 were not randomized or did not start due to the following: n=21 were screen failures, n=18 withdrew consent prior to randomization, n=4 were not randomized due to non-progression. n=4 were randomized however withdrew consent prior to treatment initiation and did not start.
Participant milestones
| Measure |
Placebo/Fulvestrant
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Overall Study
STARTED
|
60
|
62
|
|
Overall Study
COMPLETED
|
59
|
60
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Placebo/Fulvestrant
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
Study of Efficacy of Ribociclib After Progression on CDK4/6 Inhibition in Patients With HR+ HER2- Advanced Breast Cancer
Baseline characteristics by cohort
| Measure |
Placebo/Fulvestrant
n=59 Participants
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
n=60 Participants
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
Total
n=119 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59 years
n=5 Participants
|
55 years
n=7 Participants
|
57 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
48 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
59 participants
n=5 Participants
|
60 participants
n=7 Participants
|
119 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Performance Status Score 0
|
38 Score on a scale
n=5 Participants
|
40 Score on a scale
n=7 Participants
|
78 Score on a scale
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Performance Status Score 1
|
21 Score on a scale
n=5 Participants
|
20 Score on a scale
n=7 Participants
|
41 Score on a scale
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 30 monthsProgression free survival (PFS) is defined as the interval from the time of randomization until objective disease progression (local assessment) or death from any cause. Disease status will be assessed with comprehensive radiographic studies every three treatment cycles (approximately every 12 weeks (+/- 1 week)). Disease progression as assed by RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Outcome measures
| Measure |
Placebo/Fulvestrant
n=59 Participants
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
n=60 Participants
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Progression Free Survival (PFS)
|
2.76 months
Interval 2.66 to 3.25
|
5.29 months
Interval 3.02 to 8.12
|
SECONDARY outcome
Timeframe: measured every 12 weeks, up to 6 monthsPopulation: 35 placebo arm and 35 Ribociclib (LEE-011)/Fulvestrant (n=70) analyzed as these 70 participants had measurable disease.
Evaluation of disease will be made according to RECIST criteria (version 1.1) in patients with measurable disease. As this study will enroll patients with measureable and un-measurable disease as defined by RECIST v1.1, ORR will only be assessed in evaluable patients. ORR = complete response (disappearance of all target lesions; ny pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm) + partial response (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters).
Outcome measures
| Measure |
Placebo/Fulvestrant
n=35 Participants
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
n=35 Participants
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Overall Response Rate (ORR)
|
4 participants
|
7 participants
|
SECONDARY outcome
Timeframe: Up to 24 weeksCBR defined as the number of participants with complete response (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm) + partial response (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters) + stable disease (Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for disease progression, taking as reference the smallest sum of the diameters while on study) at ≥ 24 weeks of follow up per RESIST 1.1 criteria.
Outcome measures
| Measure |
Placebo/Fulvestrant
n=59 Participants
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
n=60 Participants
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Clinical Benefit Rate (CBR)
|
15 Participants
|
26 Participants
|
Adverse Events
Placebo/Fulvestrant
Serious events: 0 serious events
Other events: 59 other events
Deaths: 2 deaths
Ribociclib (LEE-011)/Fulvestrant
Serious events: 4 serious events
Other events: 60 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Placebo/Fulvestrant
n=59 participants at risk
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
n=60 participants at risk
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Infections and infestations
Lung Infection
|
0.00%
0/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
3.3%
2/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Infections and infestations
Skin Infection
|
0.00%
0/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
1.7%
1/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Infections and infestations
Kidney Infection
|
0.00%
0/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
1.7%
1/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
Other adverse events
| Measure |
Placebo/Fulvestrant
n=59 participants at risk
Placebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Fulvestrant: 500 mg injection
Placebo: 600 mg capsule (3x 200 mg capsules)
|
Ribociclib (LEE-011)/Fulvestrant
n=60 participants at risk
LEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
LEE-011: 600 mg capsule (3x 200 mg capsules)
Fulvestrant: 500 mg injection
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
22.0%
13/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
23.3%
14/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
15.3%
9/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
71.7%
43/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.1%
3/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
25.0%
15/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Investigations
Alanine aminotransferase increased
|
20.3%
12/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
16.7%
10/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Metabolism and nutrition disorders
Anorexia
|
11.9%
7/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
10.0%
6/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Investigations
Aspartate aminotransferase increased
|
28.8%
17/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
25.0%
15/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Gastrointestinal disorders
Constipation
|
8.5%
5/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
0.00%
0/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Gastrointestinal disorders
Diarrhea
|
10.2%
6/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
15.0%
9/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Investigations
QTC Prolongation
|
3.4%
2/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
13.3%
8/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
General disorders
Fatigue
|
32.2%
19/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
33.3%
20/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Nervous system disorders
Headache
|
10.2%
6/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
8.3%
5/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Vascular disorders
Hot Flashes
|
3.4%
2/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
5.0%
3/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.1%
3/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
3.3%
2/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
3/59 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
15.0%
9/60 • 30 days following the last dose of treatment, up to 2.5 years
Systematic collection of adverse events at regular investigator assessment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Neither the complete nor any part of the results of the study carried out under this protocol, nor any of the information provided by the sponsor for the purposes of performing the study, will be published or passed on to any third party without the consent of the sponsor. Any investigator involved with this study is obligated to provide the sponsor with complete test results and all data derived from the study.
- Publication restrictions are in place
Restriction type: OTHER