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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01816594
Collaborator
Breast International Group (Other), German Breast Group (Other), SOLTI Breast Cancer Research Group (Other)
50
7
2
17.5
7.1
0.4

Study Details

Study Description

Brief Summary

This randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer prior to surgery (neo-adjuvant setting).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

NeoPHOEBE evaluated the efficacy (as defined by pCR) of BKM120 (an oral PI3K inhibitor) in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled, neo-adjuvant study in women diagnosed with primary breast cancer >1.5 cm (by US or MRI) with centrally confirmed HER2 overexpression or amplification, who have not previously undergone treatment for invasive breast cancer.

Prior to the initiation of paclitaxel, there was a 6-week "biologic window" with trastuzumab plus BKM120 or placebo only. The study was conducted separately in two cohorts (PIK3CA mutated and PI3K3CA wild-type) using a two-stage approach. Within each cohort patients were randomized into one of the following treatment arms:

Arm 1: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks.

Arm 2: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks.

After completion of study treatment, patients were to have undergone definitive surgery.

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer
Actual Study Start Date :
Sep 3, 2013
Actual Primary Completion Date :
Feb 18, 2015
Actual Study Completion Date :
Feb 18, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: BKM120 + Trastuzumab + paclitaxel

BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.

Drug: BKM120
Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.
Other Names:
  • Buparsilib
  • Drug: Trastuzumab
    Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.

    Drug: Paclitaxel
    Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.

    Placebo Comparator: BKM120 PBO + Trastuzumab + paclitaxel

    BKM120 placebo in combination with trastuzumab and paclitaxel

    Drug: Trastuzumab
    Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.

    Drug: Paclitaxel
    Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.

    Drug: BKM120 Placebo
    Neoadjuvant BKM120 placebo Administered orally 100 mg/day.

    Outcome Measures

    Primary Outcome Measures

    1. Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants [After 6 weeks]

      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.

    2. Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT) [After 6 weeks]

      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.

    3. Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT) [After 6 weeks]

      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.

    Secondary Outcome Measures

    1. Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants [After week 6]

      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.

    2. Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants [After week 6]

      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.

    3. Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants [After week 6]

      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.

    4. Rate of Breast Conserving Surgery (Most Radical Surgery) [18 weeks]

      Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)

    5. Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition [After Week 6]

      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.

    6. Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition [After Week 6]

      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.

    7. Overall Objective Response Rate (ORR) Prior to Surgery for All Participants [prior to surgery]

      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.

    8. Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) [After Week 6]

      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.

    9. Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-) [After Week 6]

      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.

    10. Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) [After Week 6]

      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.

    11. Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-) [After Week 6]

      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.

    12. Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis) [18 weeks]

      This included participants at definitive surgery irrespective of lymph node status

    13. Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0) [18 weeks]

      Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patient had provided a signed study ICF prior to any screening procedure

    • Patient was a female ≥ 18 years of age

    • Patient has an ECOG performance status of 0-1

    • Patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer >2cm by clinical examination and/or

    1.5 cm confirmed by ultrasound or by MRI

    • Patient has tumor tissue available for central review of ER, HER2 and PI3K status with centrally confirmed HER2-positive disease and known PI3KCA mutation status

    • Patient has adequate bone marrow, renal and liver function

    • Patient is able to swallow and retain oral medication

    Exclusion Criteria:
    • Patient has received prior systemic treatment for currently diagnosed disease

    • Patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor

    • Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer

    • LVEF below 50% as determined by MUGA scan or ECHO

    • Patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol

    • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120

    • Patient is currently receiving warfarin or other coumarin derived anti-coagulants

    • Patient is currently receiving chronic treatment with corticosteroids or another immunosuppressive agents (standard premedication for paclitaxel and local applications allowed)

    • Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of CYP3A

    • Patient has certain scores on an anxiety and depression mood questionnaires

    • Pregnant or nursing (lactating) women or patients not willing to apply apply highly effective contraception as defined in the protocol

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Parkville Victoria Australia 3002
    2 Novartis Investigative Site Parkville Victoria Australia 3050
    3 Novartis Investigative Site Salzburg Austria 5020
    4 Novartis Investigative Site Lubeck Germany 23538
    5 Novartis Investigative Site Offenbach Germany 63069
    6 Novartis Investigative Site Sevilla Andalucia Spain 41013
    7 Novartis Investigative Site Madrid Spain 28222

    Sponsors and Collaborators

    • Novartis Pharmaceuticals
    • Breast International Group
    • German Breast Group
    • SOLTI Breast Cancer Research Group

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01816594
    Other Study ID Numbers:
    • CBKM120F2203
    First Posted:
    Mar 22, 2013
    Last Update Posted:
    Nov 14, 2019
    Last Verified:
    Oct 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    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 Detail Screened: 68 patients Randomized and analyzed (safety and efficacy): 50 patients
    Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
    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 21
    Randomized to the mt Cohort 4 4
    COMPLETED 14 23
    NOT COMPLETED 11 2

    Baseline Characteristics

    Arm/Group Title Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel Total
    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 Participants 25 25 50
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    51.1
    (11.5)
    51.3
    (11.2)
    51.2
    (11.2)
    Sex: Female, Male (Count of Participants)
    Female
    25
    100%
    25
    100%
    50
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    Caucasian/white
    21
    84%
    24
    96%
    45
    90%
    Asian/Oriental
    3
    12%
    1
    4%
    4
    8%
    Other
    1
    4%
    0
    0%
    1
    2%

    Outcome Measures

    1. Primary Outcome
    Title Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    32.0
    128%
    40.0
    160%
    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
    Statistical Test of Hypothesis p-Value 0.811
    Comments
    Method Fisher Exact
    Comments (one-sided)
    2. Primary Outcome
    Title Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 21 21
    Number (95% Confidence Interval) [Percentage of participants]
    33.3
    133.2%
    42.9
    171.6%
    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
    Statistical Test of Hypothesis p-Value 0.830
    Comments
    Method Fisher Exact
    Comments (one-sided)
    3. Primary Outcome
    Title Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 4 4
    Number (95% Confidence Interval) [Percentage of participants]
    25.0
    100%
    25.0
    100%
    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
    Statistical Test of Hypothesis p-Value 0.786
    Comments
    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
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    56.0
    224%
    44.0
    176%
    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
    Statistical Test of Hypothesis p-Value 0.286
    Comments
    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
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 21 21
    Number (95% Confidence Interval) [Percentage of participants]
    61.9
    247.6%
    42.9
    171.6%
    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
    Statistical Test of Hypothesis p-Value 0.177
    Comments
    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
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 4 4
    Number (95% Confidence Interval) [Percentage of participants]
    25.0
    100%
    50.0
    200%
    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
    Statistical Test of Hypothesis p-Value 0.929
    Comments
    Method Fisher Exact
    Comments (one-sided)
    7. Secondary Outcome
    Title Rate of Breast Conserving Surgery (Most Radical Surgery)
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    60.0
    240%
    68.0
    272%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.811
    Comments
    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
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    20.0
    80%
    28.0
    112%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.840
    Comments
    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
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    32.0
    128%
    36.0
    144%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.724
    Comments
    Method Fisher Exact
    Comments (one-sided)
    10. Secondary Outcome
    Title Overall Objective Response Rate (ORR) Prior to Surgery for All Participants
    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

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    56.0
    224%
    76.0
    304%
    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
    Statistical Test of Hypothesis p-Value 0.964
    Comments
    Method Fisher Exact
    Comments (one-sided)
    11. Secondary Outcome
    Title Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
    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

    Outcome Measure Data

    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+)
    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
    Measure Participants 16 15
    Number (95% Confidence Interval) [Percentage of participants]
    31.3
    125.2%
    26.7
    106.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments For ER+ participants - pCR
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.546
    Comments
    Method Fisher Exact
    Comments (one-sided)
    12. Secondary Outcome
    Title Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)
    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

    Outcome Measure Data

    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-)
    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
    Measure Participants 9 10
    Number (95% Confidence Interval) [Percentage of participants]
    33.3
    133.2%
    60.0
    240%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments For ER- participants - pCR
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    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+)
    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

    Outcome Measure Data

    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+)
    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
    Measure Participants 16 15
    Number (95% Confidence Interval) [Percentage of participants]
    68.8
    275.2%
    33.3
    133.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments For ER+ participants - ORR
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    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-)
    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

    Outcome Measure Data

    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-)
    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
    Measure Participants 9 10
    Number (95% Confidence Interval) [Percentage of participants]
    33.3
    133.2%
    60.0
    240%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments For ER- participants - ORR
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method Fisher Exact
    Comments (one-sided)
    15. Secondary Outcome
    Title Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)
    Description This included participants at definitive surgery irrespective of lymph node status
    Time Frame 18 weeks

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    12.0
    48%
    12.0
    48%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.666
    Comments
    Method Fisher Exact
    Comments (one-sided)
    16. Secondary Outcome
    Title Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)
    Description Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.
    Time Frame 18 weeks

    Outcome Measure Data

    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
    Arm/Group Description BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. BKM120 placebo in combination with trastuzumab and paclitaxel
    Measure Participants 25 25
    Number (95% Confidence Interval) [Percentage of participants]
    52.0
    208%
    60.0
    240%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.803
    Comments
    Method Fisher Exact
    Comments (one-sided)

    Adverse Events

    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
    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 (%) # Events Affected / at Risk (%) # Events
    Total 0/25 (0%) 0/25 (0%)
    Serious Adverse Events
    Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/25 (32%) 2/25 (8%)
    Gastrointestinal disorders
    Diarrhoea 1/25 (4%) 0/25 (0%)
    General disorders
    Catheter site pain 1/25 (4%) 0/25 (0%)
    Pyrexia 1/25 (4%) 0/25 (0%)
    Thrombosis in device 0/25 (0%) 1/25 (4%)
    Hepatobiliary disorders
    Hepatotoxicity 1/25 (4%) 0/25 (0%)
    Immune system disorders
    Hypersensitivity 1/25 (4%) 0/25 (0%)
    Infections and infestations
    Acute sinusitis 0/25 (0%) 1/25 (4%)
    Pneumonia 1/25 (4%) 0/25 (0%)
    Investigations
    Hepatic enzyme increased 2/25 (8%) 0/25 (0%)
    Nervous system disorders
    Headache 0/25 (0%) 1/25 (4%)
    Psychiatric disorders
    Mental disorder 1/25 (4%) 0/25 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema 1/25 (4%) 0/25 (0%)
    Other (Not Including Serious) Adverse Events
    Trastuzumab + BKM120 + Paclitaxel Trastuzumab + BKM120 PBO + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/25 (84%) 19/25 (76%)
    Blood and lymphatic system disorders
    Anemia 17/25 (68%) 18/25 (72%)
    Leukopenia 11/25 (44%) 15/25 (60%)
    Lymphopenia 11/25 (44%) 8/25 (32%)
    Neutropenia 6/25 (24%) 9/25 (36%)
    Thrombopenia 4/25 (16%) 0/25 (0%)
    Cardiac disorders
    Cardiac disorders not yet listed 1/25 (4%) 3/25 (12%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders 1/25 (4%) 2/25 (8%)
    Eye disorders
    Eye disorders 5/25 (20%) 3/25 (12%)
    Gastrointestinal disorders
    Abdominal pain 2/25 (8%) 4/25 (16%)
    Constipation 4/25 (16%) 7/25 (28%)
    Diarrhea 15/25 (60%) 10/25 (40%)
    Dysgeusia 4/25 (16%) 5/25 (20%)
    Dyspepsia 4/25 (16%) 4/25 (16%)
    Mucositis 19/25 (76%) 12/25 (48%)
    Nausea 11/25 (44%) 8/25 (32%)
    Other gastrointestinal disorders 7/25 (28%) 7/25 (28%)
    Upper abdominal pain 5/25 (20%) 1/25 (4%)
    Vomiting 3/25 (12%) 2/25 (8%)
    General disorders
    Chills 1/25 (4%) 4/25 (16%)
    Fatigue 13/25 (52%) 14/25 (56%)
    Oedema 3/25 (12%) 8/25 (32%)
    Other general disorders and administration site conditions 2/25 (8%) 1/25 (4%)
    Immune system disorders
    Allergic reactions 3/25 (12%) 1/25 (4%)
    Infections and infestations
    Fever without neutropenia 7/25 (28%) 3/25 (12%)
    Infection 12/25 (48%) 19/25 (76%)
    Injury, poisoning and procedural complications
    Injury and poisoning and procedural complications 1/25 (4%) 2/25 (8%)
    Investigations
    Decreased calcium 9/25 (36%) 11/25 (44%)
    Decreased potassium 6/25 (24%) 2/25 (8%)
    Decreased serum albumin 5/25 (20%) 2/25 (8%)
    Decreased sodium 9/25 (36%) 7/25 (28%)
    Increased ALT 21/25 (84%) 18/25 (72%)
    Increased AP 6/25 (24%) 6/25 (24%)
    Increased AST 19/25 (76%) 9/25 (36%)
    Increased FPG 13/25 (52%) 8/25 (32%)
    Increased GGT 8/25 (32%) 7/25 (28%)
    Increased aPTT 5/25 (20%) 6/25 (24%)
    Increased potassium 3/25 (12%) 11/25 (44%)
    Increased serum creatinine 1/25 (4%) 2/25 (8%)
    Increased sodium 4/25 (16%) 2/25 (8%)
    Increased total bilirubin 2/25 (8%) 0/25 (0%)
    Increased total cholesterol 14/25 (56%) 14/25 (56%)
    Increased triglycerides 5/25 (20%) 6/25 (24%)
    Increased uric acid 6/25 (24%) 10/25 (40%)
    Metabolism and nutrition disorders
    Anorexia 5/25 (20%) 1/25 (4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/25 (28%) 10/25 (40%)
    Bone pain 3/25 (12%) 5/25 (20%)
    Myalgia 3/25 (12%) 5/25 (20%)
    Other musculo-skeletal and connective tissue disorders 2/25 (8%) 1/25 (4%)
    Nervous system disorders
    Dizziness 9/25 (36%) 4/25 (16%)
    Headache 2/25 (8%) 8/25 (32%)
    Other neurological disorder 3/25 (12%) 2/25 (8%)
    Peripheral sensory neuropathy 14/25 (56%) 16/25 (64%)
    Psychiatric disorders
    Anxiety 5/25 (20%) 3/25 (12%)
    Depression 6/25 (24%) 8/25 (32%)
    Insomnia 3/25 (12%) 4/25 (16%)
    Psychiatric disorders 2/25 (8%) 0/25 (0%)
    Renal and urinary disorders
    Renal and urinary disorders 2/25 (8%) 0/25 (0%)
    Reproductive system and breast disorders
    Reproductive system and breast disorders 1/25 (4%) 3/25 (12%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 2/25 (8%) 6/25 (24%)
    Epistaxis 0/25 (0%) 5/25 (20%)
    Other respiratory and mediastinal disorders 5/25 (20%) 6/25 (24%)
    Skin and subcutaneous tissue disorders
    Alopecia 18/25 (72%) 17/25 (68%)
    Dry skin 5/25 (20%) 4/25 (16%)
    Erythema 3/25 (12%) 5/25 (20%)
    Nail disorder 5/25 (20%) 5/25 (20%)
    Other skin and subcutaneous tissue disorders 5/25 (20%) 7/25 (28%)
    Pruritus 10/25 (40%) 5/25 (20%)
    Rash maculo-papular 15/25 (60%) 12/25 (48%)
    Rash other than macular-papular or NOS 8/25 (32%) 8/25 (32%)
    Vascular disorders
    Hot flushes 5/25 (20%) 7/25 (28%)
    Vascular disorders 1/25 (4%) 3/25 (12%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email trialandresults.registries@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01816594
    Other Study ID Numbers:
    • CBKM120F2203
    First Posted:
    Mar 22, 2013
    Last Update Posted:
    Nov 14, 2019
    Last Verified:
    Oct 1, 2019