Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer

This study has been terminated.
(Due to the rare patient population and challenges to enroll patients.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01132664
First received: May 7, 2010
Last updated: August 9, 2016
Last verified: August 2016
Results First Received: August 4, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Metastatic Breast Cancer
HER2+ Breast Cancer
Interventions: Drug: BKM120
Drug: Trastuzumab
Drug: Capecitabine

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
72 patients (pts) were enrolled: 18 in ph lb, 53 in ph ll, including 8 from ph lb, with 45 new pts in ph ll & 9 in the brain metastasis (BM) cohort. Of the 72 pts, 1 in ph lb & 3 in phase ll, did not receive Burparlisib, only Trastuzumab. Therefore, 68 patients (17 in ph l, 42 in ph ll, 9 in BM cohort) were treated with buparlisib + trastuzumab.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Primary outcome measure for BM cohort was MTD/RP2D which was not reached/established due to premature termination of the study.

Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR) & Progression Free Survival (PFS)were not calculated for the BM cohort either.


Reporting Groups
  Description
Phase Ib - 50 mg Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
Phase Ib - 100mg Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
Phase II - 100mg Patients in the phase II expansion + patients from phase Ib dose escalation were included in phase II and received 100 mg of investigational drug - buparsilib
BM Cohort - 80mg Patients in the BM cohort who received 80 mg of buparlisib - investigational drug
BM Cohort - 100mg Patients in the BM cohort who received 100 mg of buparlisib - investigational drug

Participant Flow for 3 periods

Period 1:   Phase lb
    Phase Ib - 50 mg     Phase Ib - 100mg     Phase II - 100mg     BM Cohort - 80mg     BM Cohort - 100mg  
STARTED     5     12     0     0     0  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     5     12     0     0     0  
Adverse Event                 0                 1                 0                 0                 0  
Withdrawal by Subject                 1                 2                 0                 0                 0  
Disease Progression                 4                 9                 0                 0                 0  

Period 2:   Phase ll
    Phase Ib - 50 mg     Phase Ib - 100mg     Phase II - 100mg     BM Cohort - 80mg     BM Cohort - 100mg  
STARTED     0     0     50 [1]   0     0  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     0     0     50     0     0  
Death                 0                 0                 2                 0                 0  
Adverse Event                 0                 0                 10                 0                 0  
Withdrawal by Subject                 0                 0                 3                 0                 0  
Disease progression                 0                 0                 35                 0                 0  
[1] Of the 50 patients, 8 were from phase lb & were eligible for inclusion in Phase II

Period 3:   BM Cohort
    Phase Ib - 50 mg     Phase Ib - 100mg     Phase II - 100mg     BM Cohort - 80mg     BM Cohort - 100mg  
STARTED     0     0     0     3     6  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     0     0     0     3     6  
Disease progression                 0                 0                 0                 3                 4  
Adverse Event                 0                 0                 0                 0                 1  
Withdrawal by Subject                 0                 0                 0                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase Ib - 50 mg Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
Phase Ib - 100mg Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
Phase II - 100mg Patients in the phase II only expansion cohort who received 100 mg of buparlisib - investigational drug
BM Cohort - 80mg Patients in the BM cohort who received 80 mg of buparlisib - investigational drug
BM Cohort - 100mg Patients in the BM cohort who received 100 mg of buparlisib - investigational drug
Total Total of all reporting groups

Baseline Measures
    Phase Ib - 50 mg     Phase Ib - 100mg     Phase II - 100mg     BM Cohort - 80mg     BM Cohort - 100mg     Total  
Number of Participants  
[units: participants]
  5     12     42     3     6     68  
Age, Customized  
[units: Participants]
           
<65 years     5     11     35     3     6     60  
>=65 years     0     1     7     0     0     8  
Gender  
[units: Participants]
           
Female     5     12     42     3     6     68  
Male     0     0     0     0     0     0  
Female: Child bearing potential  
[units: Participants]
           
Able to bear children     2     3     8     1     1     15  
Premenarche     0     0     0     0     0     0  
Post-menopausal     3     8     31     2     4     48  
Sterile - of child bearing age     0     1     3     0     1     5  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Dose Limiting Toxicity (DLT) - Phase l Only   [ Time Frame: cycle 1 - 28 days ]

2.  Primary:   Overall Response Rate (ORR) - Phase ll   [ Time Frame: 18 months ]

3.  Secondary:   Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll   [ Time Frame: 18 months ]

4.  Secondary:   Clinical Benefit Rate (CBR) - Phase l & ll   [ Time Frame: 18 months ]

5.  Secondary:   Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll   [ Time Frame: 18 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registry@novartis.com



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01132664     History of Changes
Other Study ID Numbers: CBKM120X2107
2009-015417-46 ( EudraCT Number )
Study First Received: May 7, 2010
Results First Received: August 4, 2015
Last Updated: August 9, 2016
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Agence nationale de sécurité du médicament et des produits de santé (ANSM)
Italy: The Italian Medicines Agency
Spain: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency