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NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer (NeoPHOEBE)

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ClinicalTrials.gov Identifier: NCT01816594
Recruitment Status : Completed
First Posted : March 22, 2013
Results First Posted : November 14, 2019
Last Update Posted : November 14, 2019
Sponsor:
Collaborators:
Breast International Group
German Breast Group
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition HER2-positive Newly Diagnosed, Primary Breast Cancer
Interventions Drug: BKM120
Drug: Trastuzumab
Drug: Paclitaxel
Drug: BKM120 Placebo
Enrollment 50
Recruitment Details Planned: Minimum 128 patients (in case of early stopping of both cohorts), maximum: 220 patients (if both cohorts would have proceeded into stage 2), and 174 patients if one cohort would have stopped early.
Pre-assignment Details Screened: 68 patients Randomized and analyzed (safety and efficacy): 50 patients
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
Period Title: Overall Study
Started 25 25
Randomized to the wt Cohort 21 [1] 21 [1]
Randomized to the mt Cohort 4 [2] 4 [2]
Completed 14 23
Not Completed 11 2
Reason Not Completed
Local Progress             0             2
Adverse Event             9             0
Withdrawal by Subject             1             0
Physician Decision             1             0
[1]
wt = PIK3CA wild-type
[2]
mt = PIK3CA mutant
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel Total
Hide Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel Total of all reporting groups
Overall Number of Baseline Participants 25 25 50
Hide Baseline Analysis Population Description
All randomized patients (N=50) were included in the intention-to-treat set and in the safety analysis set, since all patients started study treatment. Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 25 participants 50 participants
51.1  (11.5) 51.3  (11.2) 51.2  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
Female
25
 100.0%
25
 100.0%
50
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 25 participants 25 participants 50 participants
Caucasian/white 21 24 45
Asian/Oriental 3 1 4
Other 1 0 1
1.Primary Outcome
Title Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
Hide Description Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Time Frame After 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
32.0
(14.9 to 53.5)
40.0
(21.1 to 61.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments All participantss
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.811
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
2.Primary Outcome
Title Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
Hide Description Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Time Frame After 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 21 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
33.3
(14.6 to 57.0)
42.9
(21.8 to 66.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments wild type cohort
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.830
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
3.Primary Outcome
Title Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
Hide Description Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Time Frame After 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 4 4
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
25.0
(0.6 to 80.6)
25.0
(0.6 to 80.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments mutant cohort
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.786
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
4.Secondary Outcome
Title Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants
Hide Description Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
Time Frame After week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
56.0
(34.9 to 75.6)
44.0
(24.4 to 65.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments All participants
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.286
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
5.Secondary Outcome
Title Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants
Hide Description Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
Time Frame After week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 21 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
61.9
(38.4 to 81.9)
42.9
(21.8 to 66.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments wild type cohort
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
6.Secondary Outcome
Title Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants
Hide Description Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
Time Frame After week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 4 4
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
25.0
(0.6 to 80.6)
50.0
(6.8 to 93.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments mutant cohort
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.929
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
7.Secondary Outcome
Title Rate of Breast Conserving Surgery (Most Radical Surgery)
Hide Description Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)
Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
60.0
(38.7 to 78.9)
68.0
(46.5 to 85.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.811
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
8.Secondary Outcome
Title Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition
Hide Description Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines.
Time Frame After Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
20.0
(6.8 to 40.7)
28.0
(12.1 to 49.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.840
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
9.Secondary Outcome
Title Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition
Hide Description Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions.
Time Frame After Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
32.0
(14.9 to 53.5)
36.0
(18.0 to 57.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.724
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
10.Secondary Outcome
Title Overall Objective Response Rate (ORR) Prior to Surgery for All Participants
Hide Description Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
Time Frame prior to surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
56.0
(34.9 to 75.6)
76.0
(54.9 to 90.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments All participants
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.964
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
11.Secondary Outcome
Title Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Hide Description pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.
Time Frame After Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel ( ER+) Trastuzumab + BKM120 PBO + Paclitaxel (ER+)
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in positive estrogen receptor participants.
BKM120 placebo in combination with trastuzumab and paclitaxel in patients with positive estrogen receptor participants
Overall Number of Participants Analyzed 16 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
31.3
(11.0 to 58.7)
26.7
(7.8 to 55.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel ( ER+), Trastuzumab + BKM120 PBO + Paclitaxel (ER+)
Comments For ER+ participants - pCR
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.546
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
12.Secondary Outcome
Title Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)
Hide Description pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.
Time Frame After Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel (ER-) Trastuzumab + BKM120 PBO + Paclitaxel (ER-)
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in negative estrogen receptor participants.
BKM120 placebo in combination with trastuzumab and paclitaxel in negative estrogen receptor participants
Overall Number of Participants Analyzed 9 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
33.3
(7.5 to 70.1)
60.0
(26.2 to 87.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel (ER-), Trastuzumab + BKM120 PBO + Paclitaxel (ER-)
Comments For ER- participants - pCR
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.949
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
13.Secondary Outcome
Title Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Hide Description Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
Time Frame After Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel (ER+) Trastuzumab + BKM120 PBO + Paclitaxel (ER+)
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in positive estrogen receptor participants.
BKM120 placebo in combination with trastuzumab and paclitaxel in positive estrogen receptor participants
Overall Number of Participants Analyzed 16 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
68.8
(41.3 to 89.0)
33.3
(11.8 to 61.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel (ER+), Trastuzumab + BKM120 PBO + Paclitaxel (ER+)
Comments For ER+ participants - ORR
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.053
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
14.Secondary Outcome
Title Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)
Hide Description Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
Time Frame After Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel (ER-) Trastuzumab + BKM120 PBO + Paclitaxel (ER-)
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in negative estrogen receptor participants.
BKM120 placebo in combination with trastuzumab and paclitaxel in negative estrogen receptor participants
Overall Number of Participants Analyzed 9 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
33.3
(7.5 to 70.1)
60.0
(26.2 to 87.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel (ER-), Trastuzumab + BKM120 PBO + Paclitaxel (ER-)
Comments For ER- participants - ORR
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.949
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
15.Secondary Outcome
Title Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)
Hide Description This included participants at definitive surgery irrespective of lymph node status
Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
12.0
(2.5 to 31.2)
12.0
(2.5 to 31.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.666
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
16.Secondary Outcome
Title Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)
Hide Description Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.
Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description:
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
52.0
(31.3 to 72.2)
60.0
(38.7 to 78.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.803
Comments [Not Specified]
Method Fisher Exact
Comments (one-sided)
Time Frame AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Adverse Event Reporting Description All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
 
Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Hide Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
All-Cause Mortality
Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/25 (0.00%) 
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Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   8/25 (32.00%)   2/25 (8.00%) 
Gastrointestinal disorders     
Diarrhoea † 1  1/25 (4.00%)  0/25 (0.00%) 
General disorders     
Catheter site pain † 1  1/25 (4.00%)  0/25 (0.00%) 
Pyrexia † 1  1/25 (4.00%)  0/25 (0.00%) 
Thrombosis in device † 1  0/25 (0.00%)  1/25 (4.00%) 
Hepatobiliary disorders     
Hepatotoxicity † 1  1/25 (4.00%)  0/25 (0.00%) 
Immune system disorders     
Hypersensitivity † 1  1/25 (4.00%)  0/25 (0.00%) 
Infections and infestations     
Acute sinusitis † 1  0/25 (0.00%)  1/25 (4.00%) 
Pneumonia † 1  1/25 (4.00%)  0/25 (0.00%) 
Investigations     
Hepatic enzyme increased † 1  2/25 (8.00%)  0/25 (0.00%) 
Nervous system disorders     
Headache † 1  0/25 (0.00%)  1/25 (4.00%) 
Psychiatric disorders     
Mental disorder † 1  1/25 (4.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary oedema † 1  1/25 (4.00%)  0/25 (0.00%) 
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   21/25 (84.00%)   19/25 (76.00%) 
Blood and lymphatic system disorders     
Anemia † 1  17/25 (68.00%)  18/25 (72.00%) 
Leukopenia † 1  11/25 (44.00%)  15/25 (60.00%) 
Lymphopenia † 1  11/25 (44.00%)  8/25 (32.00%) 
Neutropenia † 1  6/25 (24.00%)  9/25 (36.00%) 
Thrombopenia † 1  4/25 (16.00%)  0/25 (0.00%) 
Cardiac disorders     
Cardiac disorders not yet listed † 1  1/25 (4.00%)  3/25 (12.00%) 
Ear and labyrinth disorders     
Ear and labyrinth disorders † 1  1/25 (4.00%)  2/25 (8.00%) 
Eye disorders     
Eye disorders † 1  5/25 (20.00%)  3/25 (12.00%) 
Gastrointestinal disorders     
Abdominal pain † 1  2/25 (8.00%)  4/25 (16.00%) 
Constipation † 1  4/25 (16.00%)  7/25 (28.00%) 
Diarrhea † 1  15/25 (60.00%)  10/25 (40.00%) 
Dysgeusia † 1  4/25 (16.00%)  5/25 (20.00%) 
Dyspepsia † 1  4/25 (16.00%)  4/25 (16.00%) 
Mucositis † 1  19/25 (76.00%)  12/25 (48.00%) 
Nausea † 1  11/25 (44.00%)  8/25 (32.00%) 
Other gastrointestinal disorders † 1  7/25 (28.00%)  7/25 (28.00%) 
Upper abdominal pain † 1  5/25 (20.00%)  1/25 (4.00%) 
Vomiting † 1  3/25 (12.00%)  2/25 (8.00%) 
General disorders     
Chills † 1  1/25 (4.00%)  4/25 (16.00%) 
Fatigue † 1  13/25 (52.00%)  14/25 (56.00%) 
Oedema † 1  3/25 (12.00%)  8/25 (32.00%) 
Other general disorders and administration site conditions † 1  2/25 (8.00%)  1/25 (4.00%) 
Immune system disorders     
Allergic reactions † 1  3/25 (12.00%)  1/25 (4.00%) 
Infections and infestations     
Fever without neutropenia † 1  7/25 (28.00%)  3/25 (12.00%) 
Infection † 1  12/25 (48.00%)  19/25 (76.00%) 
Injury, poisoning and procedural complications     
Injury and poisoning and procedural complications † 1  1/25 (4.00%)  2/25 (8.00%) 
Investigations     
Decreased calcium † 1  9/25 (36.00%)  11/25 (44.00%) 
Decreased potassium † 1  6/25 (24.00%)  2/25 (8.00%) 
Decreased serum albumin † 1  5/25 (20.00%)  2/25 (8.00%) 
Decreased sodium † 1  9/25 (36.00%)  7/25 (28.00%) 
Increased ALT † 1  21/25 (84.00%)  18/25 (72.00%) 
Increased AP † 1  6/25 (24.00%)  6/25 (24.00%) 
Increased AST † 1  19/25 (76.00%)  9/25 (36.00%) 
Increased FPG † 1  13/25 (52.00%)  8/25 (32.00%) 
Increased GGT † 1  8/25 (32.00%)  7/25 (28.00%) 
Increased aPTT † 1  5/25 (20.00%)  6/25 (24.00%) 
Increased potassium † 1  3/25 (12.00%)  11/25 (44.00%) 
Increased serum creatinine † 1  1/25 (4.00%)  2/25 (8.00%) 
Increased sodium † 1  4/25 (16.00%)  2/25 (8.00%) 
Increased total bilirubin † 1  2/25 (8.00%)  0/25 (0.00%) 
Increased total cholesterol † 1  14/25 (56.00%)  14/25 (56.00%) 
Increased triglycerides † 1  5/25 (20.00%)  6/25 (24.00%) 
Increased uric acid † 1  6/25 (24.00%)  10/25 (40.00%) 
Metabolism and nutrition disorders     
Anorexia † 1  5/25 (20.00%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  7/25 (28.00%)  10/25 (40.00%) 
Bone pain † 1  3/25 (12.00%)  5/25 (20.00%) 
Myalgia † 1  3/25 (12.00%)  5/25 (20.00%) 
Other musculo-skeletal and connective tissue disorders † 1  2/25 (8.00%)  1/25 (4.00%) 
Nervous system disorders     
Dizziness † 1  9/25 (36.00%)  4/25 (16.00%) 
Headache † 1  2/25 (8.00%)  8/25 (32.00%) 
Other neurological disorder † 1  3/25 (12.00%)  2/25 (8.00%) 
Peripheral sensory neuropathy † 1  14/25 (56.00%)  16/25 (64.00%) 
Psychiatric disorders     
Anxiety † 1  5/25 (20.00%)  3/25 (12.00%) 
Depression † 1  6/25 (24.00%)  8/25 (32.00%) 
Insomnia † 1  3/25 (12.00%)  4/25 (16.00%) 
Psychiatric disorders † 1  2/25 (8.00%)  0/25 (0.00%) 
Renal and urinary disorders     
Renal and urinary disorders † 1  2/25 (8.00%)  0/25 (0.00%) 
Reproductive system and breast disorders     
Reproductive system and breast disorders † 1  1/25 (4.00%)  3/25 (12.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea † 1  2/25 (8.00%)  6/25 (24.00%) 
Epistaxis † 1  0/25 (0.00%)  5/25 (20.00%) 
Other respiratory and mediastinal disorders † 1  5/25 (20.00%)  6/25 (24.00%) 
Skin and subcutaneous tissue disorders     
Alopecia † 1  18/25 (72.00%)  17/25 (68.00%) 
Dry skin † 1  5/25 (20.00%)  4/25 (16.00%) 
Erythema † 1  3/25 (12.00%)  5/25 (20.00%) 
Nail disorder † 1  5/25 (20.00%)  5/25 (20.00%) 
Other skin and subcutaneous tissue disorders † 1  5/25 (20.00%)  7/25 (28.00%) 
Pruritus † 1  10/25 (40.00%)  5/25 (20.00%) 
Rash maculo-papular † 1  15/25 (60.00%)  12/25 (48.00%) 
Rash other than macular-papular or NOS † 1  8/25 (32.00%)  8/25 (32.00%) 
Vascular disorders     
Hot flushes † 1  5/25 (20.00%)  7/25 (28.00%) 
Vascular disorders † 1  1/25 (4.00%)  3/25 (12.00%) 
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
[Not Specified]
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 (i.e., data from all sites) in the clinical trial.
Results Point of Contact
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Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01816594    
Other Study ID Numbers: CBKM120F2203
First Submitted: March 14, 2013
First Posted: March 22, 2013
Results First Submitted: July 11, 2016
Results First Posted: November 14, 2019
Last Update Posted: November 14, 2019