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A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi (BELLE-3)

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: NCT01633060
Recruitment Status : Terminated (Novartis decided not to pursue further development of buparlisib program (assessment of moderate PFS benefit with know, but manageable, buparlisib profile).)
First Posted : July 4, 2012
Results First Posted : January 9, 2019
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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: BKM120
Drug: BKM120 matching placebo
Enrollment 432
Recruitment Details This study was conducted at 201 centers in 22 countries worldwide (Argentina, Austria, Belgium, Bulgaria, Canada, Colombia, Finland, France, Germany, Greece, Hungary, Italy, Republic of Korea, Lebanon, The Netherlands, Norway, Poland, Spain, Sweden, Thailand, UK and USA).
Pre-assignment Details At least 420 patients were planned to be enrolled, randomized in a 2:1 ratio (two buparlisib, one placebo). A total of 432 patients were actually enrolled and analyzed (buparlisib arm: N=289; placebo arm: N=143). Not completed: in Randomization Phase=Randomized and not Treated; in Treatment Phase=Discontinued study treatment per Protocol.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Period Title: Randomization Phase
Started [1] 289 [1] 143 [1]
Completed [2] 288 140
Not Completed 1 3
Reason Not Completed
Protocol deviation             1             2
Technical problem             0             1
[1]
All randomized patients
[2]
Randomized and treated
Period Title: Treatment Phase
Started [1] 288 140
FAS - ctDNA PIK3CA Mutant [2] 100 35
FAS - ctDNA PIK3CA Non-mutant [3] 132 81
Safety Set (SS) [4] 288 140
Pharmacokinetic Analysis Set (PAS) [5] 63 0
Completed 0 0
Not Completed 288 140
Reason Not Completed
Adverse Event             24             3
Lost to Follow-up             1             0
Physician Decision             16             7
Progressive Disease             210             120
Protocol Deviation             1             0
Study Terminated by sponsor             7             3
Subject/guardian decision             25             4
Death             4             3
[1]
All patients in FAS that were treated
[2]
All patients in FAS with ctDNA sample and PIK3CA mutation
[3]
All patients in FAS with ctDNA sample and no PIK3CA mutation
[4]
At least 1 dose of study treatment and a 1 post baseline safety assessment
[5]
At least one dose of Buparlisib and had at least 1 evaluable buparlisib concentration measurement
Period Title: Post-Treatment Efficacy Follow-Up Phase
Started [1] 16 [2] 2 [2]
Completed 0 0
Not Completed 16 2
Reason Not Completed
Adverse Event             2             0
Physician Decision             1             0
Progressive Disease             10             1
Study terminated by sponsor             1             0
Subject/Guardian Decision             1             1
Death             1             0
[1]
All patients who discontinued treatment and entered Post-Treatment Efficacy Follow-Up Phase
[2]
All patients who entered Post-Treatment Efficacy Fup Phase
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant Total
Hide Arm/Group Description BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. Total of all reporting groups
Overall Number of Baseline Participants 289 143 432
Hide Baseline Analysis Population Description
Full Analysis Set (FAS)
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 289 participants 143 participants 432 participants
60.5  (9.76) 61.5  (9.23) 60.8  (9.59)
[1]
Measure Analysis Population Description: Full Analysis Set (FAS)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 289 participants 143 participants 432 participants
Female
289
 100.0%
143
 100.0%
432
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Full Analysis Set (FAS)
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 289 participants 143 participants 432 participants
American Indian or Alaska Native
4
   1.4%
1
   0.7%
5
   1.2%
Asian
20
   6.9%
9
   6.3%
29
   6.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   1.4%
4
   2.8%
8
   1.9%
White
249
  86.2%
121
  84.6%
370
  85.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
12
   4.2%
8
   5.6%
20
   4.6%
[1]
Measure Analysis Population Description: Full Analysis Set (FAS)
1.Primary Outcome
Title Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)
Hide Description Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization.
Time Frame Every 6 weeks after randomization up to a maximum of 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) based on Primary Analysis.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Median (95% Confidence Interval)
Unit of Measure: Months
3.9
(2.8 to 4.2)
1.8
(1.5 to 2.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of progression-free survival (PFS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (1-Sided) 95%
0.53
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS) - Full Analysis Set (FAS)
Hide Description Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up.
Time Frame Every 6 weeks after randomization up to a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) based on Primary Analysis.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Median (95% Confidence Interval)
Unit of Measure: Months
21.2
(18.2 to 23.4)
22.1 [1] 
(17.3 to NA)
[1]
NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)
3.Secondary Outcome
Title Progression Free Survival (PFS) by PIK3CA Mutational Status
Hide Description Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization.
Time Frame Every 6 weeks after randomization up to a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Median (95% Confidence Interval)
Unit of Measure: Months
FAS ctDNA PIK3CA mutant Number Analyzed 100 participants 35 participants
4.2
(2.8 to 6.7)
1.6
(1.4 to 2.8)
FAS ctDNA PIK3CA non-mutant Number Analyzed 132 participants 81 participants
3.9
(2.8 to 4.3)
2.7
(1.5 to 3.6)
4.Secondary Outcome
Title Overall Survival (OS) by PIK3CA Mutational Status
Hide Description Overall Survival (OS) by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up.
Time Frame Every 6 weeks after randomization up to a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Median (95% Confidence Interval)
Unit of Measure: Months
FAS ctDNA PIK3CA mutant Number Analyzed 100 participants 35 participants
21.8
(14.7 to 25.8)
NA [1] 
(14.5 to NA)
FAS ctDNA PIK3CA non-mutant Number Analyzed 132 participants 81 participants
21.4 [1] 
(17.3 to NA)
21.4 [1] 
(17.3 to NA)
[1]
NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)
5.Secondary Outcome
Title Overall Response Rate (ORR) by PIK3CA Mutational Status
Hide Description Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization.
Time Frame Every 6 weeks after randomization up to a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Full Analysis Set (FAS) Number Analyzed 289 participants 143 participants
7.6
(4.8 to 11.3)
2.1
(0.4 to 6.0)
FAS ctDNA PIK3CA mutant Number Analyzed 100 participants 35 participants
10.0
(4.9 to 17.6)
0
(0.0 to 10.0)
FAS ctDNA PIK3CA non-mutant Number Analyzed 132 participants 81 participants
7.6
(3.7 to 13.5)
3.7
(0.8 to 10.4)
6.Secondary Outcome
Title Clinical Benefit Rate (CBR) by PIK3CA Mutational Status
Hide Description Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization.
Time Frame Week 14, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
CBR>=14wks(FAS) Number Analyzed 289 participants 143 participants
33.2
(27.8 to 39.0)
20.3
(14.0 to 27.8)
CBR>=24wks(FAS) Number Analyzed 289 participants 143 participants
24.6
(19.7 to 29.9)
15.4
(9.9 to 22.4)
CBR>=14wks(FAS ctDNA PIK3CA mutant) Number Analyzed 100 participants 35 participants
38.0
(28.5 to 48.3)
14.3
(4.8 to 30.3)
CBR>=24wks(FAS ctDNA PIK3CA mutant) Number Analyzed 100 participants 35 participants
30.0
(21.2 to 40.0)
11.4
(3.2 to 26.7)
CBR>=14wks(FAS ctDNA PIK3CA non-mutant) Number Analyzed 132 participants 81 participants
36.4
(28.2 to 45.2)
21.0
(12.7 to 31.5)
CBR>= 24wks(FAS ctDNA PIK3CA non-mutant) Number Analyzed 132 participants 81 participants
25.8
(18.5 to 34.1)
14.8
(7.9 to 24.4)
7.Secondary Outcome
Title Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS)
Hide Description Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths.
Time Frame From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set (SS) based on Final Analysis
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 288 140
Measure Type: Number
Unit of Measure: Percentage of Participants
AEs 97.9 92.9
SAEs 25.7 18.6
Deaths 42.7 48.6
8.Secondary Outcome
Title Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS)
Hide Description Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample).
Time Frame C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS) based on Primary Analysis
Arm/Group Title BKM120 100mg + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 63
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
C1D1 - 1 hour post dose
425.178
(149.6%)
C1D1 - 2 hour post dose
615.441
(70.9%)
C1D1 - 6 hour post dose
314.094
(41.9%)
C1D1 - 9 hour post dose
302.899
(58.3%)
9.Secondary Outcome
Title Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)
Hide Description Pre-dose samples were collected for trough concentrations at Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1.
Time Frame C1D15, C2D1, C3D1 and C4D1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS) based on Primary Analysis
Arm/Group Title BKM120 100mg + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 63
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
C1D15
939.978
(36.8%)
C2D1
880.074
(38.4%)
C3D1
777.026
(131.0%)
C4D1
1088.074
(27.0%)
10.Secondary Outcome
Title Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS)
Hide Description The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL.
Time Frame Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis (FAS) based on Primary Analysis
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Median (95% Confidence Interval)
Unit of Measure: Months
EORTC QLQ-30 - Global QoL score
5.3
(4.4 to 8.1)
6.3
(3.0 to 9.9)
EORTC QLQ-30 - PF scale score
11.8 [1] 
(8.1 to NA)
10.1
(7.5 to 14.6)
EORTC QLQ-30 - EF scale score
10.0 [1] 
(6.2 to NA)
10.0 [1] 
(4.9 to NA)
EORTC QLQ-30 - SF scale score
10.0
(6.2 to 20.2)
11.5
(6.4 to 14.6)
[1]
NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)
11.Secondary Outcome
Title Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS)
Hide Description The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration.
Time Frame Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis (FAS) based on Primary Analysis
Arm/Group Title BKM120 100mg + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Number of Participants Analyzed 289 143
Median (95% Confidence Interval)
Unit of Measure: Months
18.3 [1] 
(6.9 to NA)
12.0
(6.4 to 14.2)
[1]
NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)
Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up.
Adverse Event Reporting Description Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
 
Arm/Group Title BKM120 100 mg + Fulvestrant Placebo + Fulvestrant All Patients
Hide Arm/Group Description BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol test. BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. All Patients
All-Cause Mortality
BKM120 100 mg + Fulvestrant Placebo + Fulvestrant All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   123/288 (42.71%)   68/140 (48.57%)   191/428 (44.63%) 
Hide Serious Adverse Events
BKM120 100 mg + Fulvestrant Placebo + Fulvestrant All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   74/288 (25.69%)   26/140 (18.57%)   100/428 (23.36%) 
Blood and lymphatic system disorders       
Anaemia  1  1/288 (0.35%)  1/140 (0.71%)  2/428 (0.47%) 
Febrile neutropenia  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Haemolytic anaemia  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Cardiac disorders       
Angina pectoris  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Atrial fibrillation  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Cardiac arrest  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Cardiac failure acute  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Cardiac tamponade  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Intracardiac mass  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Pericardial effusion  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Ear and labyrinth disorders       
Vertigo  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Eye disorders       
Amaurosis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Diplopia  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Eyelid ptosis  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Optic atrophy  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Vision blurred  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Gastrointestinal disorders       
Abdominal pain  1  1/288 (0.35%)  1/140 (0.71%)  2/428 (0.47%) 
Ascites  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Diarrhoea  1  3/288 (1.04%)  1/140 (0.71%)  4/428 (0.93%) 
Gastrointestinal haemorrhage  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Haematemesis  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Ileus  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Intestinal perforation  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Nausea  1  1/288 (0.35%)  2/140 (1.43%)  3/428 (0.70%) 
Oesophageal haemorrhage  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Vomiting  1  4/288 (1.39%)  1/140 (0.71%)  5/428 (1.17%) 
General disorders       
Asthenia  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Death  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Facial pain  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Fatigue  1  1/288 (0.35%)  1/140 (0.71%)  2/428 (0.47%) 
General physical health deterioration  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Malaise  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Non-cardiac chest pain  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Pyrexia  1  0/288 (0.00%)  2/140 (1.43%)  2/428 (0.47%) 
Hepatobiliary disorders       
Bile duct obstruction  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Bile duct stenosis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Hepatic function abnormal  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Hepatotoxicity  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Jaundice  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Infections and infestations       
Clostridial infection  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Clostridium difficile infection  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Cystitis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Infective thrombosis  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Peritonitis  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Pneumonia  1  4/288 (1.39%)  0/140 (0.00%)  4/428 (0.93%) 
Respiratory tract infection  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Urinary tract infection  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Viral infection  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Electric injury  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Femur fracture  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Head injury  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Spinal cord injury thoracic  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Wrist fracture  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Investigations       
Alanine aminotransferase increased  1  5/288 (1.74%)  0/140 (0.00%)  5/428 (1.17%) 
Aspartate aminotransferase increased  1  6/288 (2.08%)  0/140 (0.00%)  6/428 (1.40%) 
Gamma-glutamyltransferase increased  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Transaminases increased  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Weight decreased  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Metabolism and nutrition disorders       
Decreased appetite  1  1/288 (0.35%)  1/140 (0.71%)  2/428 (0.47%) 
Dehydration  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Diabetes mellitus inadequate control  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Hypercalcaemia  1  1/288 (0.35%)  1/140 (0.71%)  2/428 (0.47%) 
Hyperglycaemia  1  3/288 (1.04%)  0/140 (0.00%)  3/428 (0.70%) 
Hyperuricaemia  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Hyponatraemia  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Back pain  1  1/288 (0.35%)  2/140 (1.43%)  3/428 (0.70%) 
Flank pain  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Muscular weakness  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Musculoskeletal chest pain  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Musculoskeletal pain  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Osteonecrosis of jaw  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Pain in extremity  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Malignant pleural effusion  1  1/288 (0.35%)  1/140 (0.71%)  2/428 (0.47%) 
Nervous system disorders       
Cerebral haemorrhage  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Cerebrovascular accident  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Dizziness  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Epilepsy  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Horner's syndrome  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Hydrocephalus  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Loss of consciousness  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Migraine  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Neuralgia  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Neurological symptom  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Posterior reversible encephalopathy syndrome  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Presyncope  1  0/288 (0.00%)  1/140 (0.71%)  1/428 (0.23%) 
Resting tremor  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Seizure  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Syncope  1  2/288 (0.69%)  1/140 (0.71%)  3/428 (0.70%) 
Transient ischaemic attack  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Vith nerve paralysis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Vocal cord paralysis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Psychiatric disorders       
Confusional state  1  4/288 (1.39%)  1/140 (0.71%)  5/428 (1.17%) 
Disorientation  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Mania  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Mental disorder  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Mood altered  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Suicide attempt  1  3/288 (1.04%)  0/140 (0.00%)  3/428 (0.70%) 
Renal and urinary disorders       
Renal failure  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Urinary retention  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Atelectasis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Dyspnoea  1  7/288 (2.43%)  1/140 (0.71%)  8/428 (1.87%) 
Pleural effusion  1  6/288 (2.08%)  0/140 (0.00%)  6/428 (1.40%) 
Respiratory failure  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Social circumstances       
Homicide  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Vascular disorders       
Circulatory collapse  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Hypertension  1  2/288 (0.69%)  0/140 (0.00%)  2/428 (0.47%) 
Hypotension  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
Venous thrombosis  1  1/288 (0.35%)  0/140 (0.00%)  1/428 (0.23%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BKM120 100 mg + Fulvestrant Placebo + Fulvestrant All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   271/288 (94.10%)   113/140 (80.71%)   384/428 (89.72%) 
Gastrointestinal disorders       
Abdominal pain  1  16/288 (5.56%)  6/140 (4.29%)  22/428 (5.14%) 
Abdominal pain upper  1  23/288 (7.99%)  4/140 (2.86%)  27/428 (6.31%) 
Constipation  1  29/288 (10.07%)  13/140 (9.29%)  42/428 (9.81%) 
Diarrhoea  1  76/288 (26.39%)  13/140 (9.29%)  89/428 (20.79%) 
Dry mouth  1  23/288 (7.99%)  5/140 (3.57%)  28/428 (6.54%) 
Dyspepsia  1  29/288 (10.07%)  2/140 (1.43%)  31/428 (7.24%) 
Nausea  1  100/288 (34.72%)  24/140 (17.14%)  124/428 (28.97%) 
Stomatitis  1  32/288 (11.11%)  6/140 (4.29%)  38/428 (8.88%) 
Vomiting  1  27/288 (9.38%)  13/140 (9.29%)  40/428 (9.35%) 
General disorders       
Asthenia  1  52/288 (18.06%)  15/140 (10.71%)  67/428 (15.65%) 
Fatigue  1  69/288 (23.96%)  25/140 (17.86%)  94/428 (21.96%) 
Oedema peripheral  1  18/288 (6.25%)  2/140 (1.43%)  20/428 (4.67%) 
Pyrexia  1  20/288 (6.94%)  8/140 (5.71%)  28/428 (6.54%) 
Infections and infestations       
Urinary tract infection  1  15/288 (5.21%)  3/140 (2.14%)  18/428 (4.21%) 
Investigations       
Alanine aminotransferase increased  1  113/288 (39.24%)  10/140 (7.14%)  123/428 (28.74%) 
Aspartate aminotransferase increased  1  108/288 (37.50%)  14/140 (10.00%)  122/428 (28.50%) 
Gamma-glutamyltransferase increased  1  26/288 (9.03%)  5/140 (3.57%)  31/428 (7.24%) 
Weight decreased  1  27/288 (9.38%)  7/140 (5.00%)  34/428 (7.94%) 
Metabolism and nutrition disorders       
Decreased appetite  1  47/288 (16.32%)  9/140 (6.43%)  56/428 (13.08%) 
Hyperglycaemia  1  104/288 (36.11%)  4/140 (2.86%)  108/428 (25.23%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  21/288 (7.29%)  12/140 (8.57%)  33/428 (7.71%) 
Back pain  1  27/288 (9.38%)  11/140 (7.86%)  38/428 (8.88%) 
Bone pain  1  9/288 (3.13%)  11/140 (7.86%)  20/428 (4.67%) 
Muscle spasms  1  21/288 (7.29%)  5/140 (3.57%)  26/428 (6.07%) 
Pain in extremity  1  19/288 (6.60%)  10/140 (7.14%)  29/428 (6.78%) 
Nervous system disorders       
Dizziness  1  35/288 (12.15%)  10/140 (7.14%)  45/428 (10.51%) 
Dysgeusia  1  19/288 (6.60%)  4/140 (2.86%)  23/428 (5.37%) 
Headache  1  27/288 (9.38%)  15/140 (10.71%)  42/428 (9.81%) 
Tremor  1  18/288 (6.25%)  0/140 (0.00%)  18/428 (4.21%) 
Psychiatric disorders       
Anxiety  1  51/288 (17.71%)  15/140 (10.71%)  66/428 (15.42%) 
Depression  1  60/288 (20.83%)  11/140 (7.86%)  71/428 (16.59%) 
Insomnia  1  26/288 (9.03%)  11/140 (7.86%)  37/428 (8.64%) 
Mood altered  1  15/288 (5.21%)  2/140 (1.43%)  17/428 (3.97%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  27/288 (9.38%)  9/140 (6.43%)  36/428 (8.41%) 
Dyspnoea  1  22/288 (7.64%)  12/140 (8.57%)  34/428 (7.94%) 
Skin and subcutaneous tissue disorders       
Dry skin  1  22/288 (7.64%)  3/140 (2.14%)  25/428 (5.84%) 
Pruritus  1  25/288 (8.68%)  4/140 (2.86%)  29/428 (6.78%) 
Rash  1  37/288 (12.85%)  3/140 (2.14%)  40/428 (9.35%) 
Vascular disorders       
Hot flush  1  10/288 (3.47%)  11/140 (7.86%)  21/428 (4.91%) 
Hypertension  1  33/288 (11.46%)  8/140 (5.71%)  41/428 (9.58%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
The primary efficacy analysis was completed by 23May16 (primary PFS analysis cutoff date). The study was later terminated and the final safety analysis was conducted up to 08Sep17. One CRF was collecting on 21Sep2017 for survival follow up (LPLV).
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.
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 the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01633060    
Other Study ID Numbers: CBKM120F2303
2012-002571-34 ( EudraCT Number )
First Submitted: June 29, 2012
First Posted: July 4, 2012
Results First Submitted: September 20, 2018
Results First Posted: January 9, 2019
Last Update Posted: January 30, 2019