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Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women

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ClinicalTrials.gov Identifier: NCT01923168
Recruitment Status : Completed
First Posted : August 15, 2013
Results First Posted : September 14, 2018
Last Update Posted : September 14, 2018
Sponsor:
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: Breast Cancer
Interventions: Drug: alpelisib
Drug: buparlisib
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of approximately 320 patients were planned to be randomized: this was based on 60 patients per arm in each cohort (PIK3CA mutant and PIK3CA wild-type) for the alpelisib+letrozole and placebo+letrozole arms, plus the estimated number of patients randomized to buparlisib+letrozole arm at the time this arm was discontinued.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Alpelisib + Letrozole Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Buparlisib + Letrozole Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Placebo + Letrozole Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.

Participant Flow:   Overall Study
    Alpelisib + Letrozole   Buparlisib + Letrozole   Placebo + Letrozole
STARTED   131   83   126 
COMPLETED   94   44   109 
NOT COMPLETED   37   39   17 
Protocol Violation                1                1                0 
Subject/guardian decision                14                14                4 
Adverse Event                12                12                0 
Physician Decision                6                9                5 
Progressive disease                4                3                7 
Death                0                0                1 



  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.
The Full Analysis Set (FAS) comprised all randomized subjects in the study.

Reporting Groups
  Description
Alpelisib + Letrozole Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Buparlisib + Letrozole Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Placebo + Letrozole Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Total Total of all reporting groups

Baseline Measures
   Alpelisib + Letrozole   Buparlisib + Letrozole   Placebo + Letrozole   Total 
Overall Participants Analyzed 
[Units: Participants]
 131   83   126   340 
Age 
[Units: Years]
Mean (Standard Deviation)
 64.3  (8.53)   65.2  (8.61)   63.1  (8.31)   64.1  (8.49) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      131 100.0%      83 100.0%      126 100.0%      340 100.0% 
Male      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
White   117   68   105   290 
Asian   7   4   10   21 
Black or African American   3   3   5   11 
Other   3   6   3   12 
Unknown   1   2   3   6 


  Outcome Measures

1.  Primary:   Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort   [ Time Frame: After 24 weeks of treatment ]

2.  Primary:   Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort   [ Time Frame: After 24 weeks of treatment ]

3.  Primary:   Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort   [ Time Frame: After 24 weeks of treatment ]

4.  Primary:   Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort   [ Time Frame: After 24 weeks of treatment ]

5.  Secondary:   pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Mutant Cohort Based on ctDNA   [ Time Frame: After 24 weeks of treatment ]

6.  Secondary:   pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Wild-type Cohort Based on ctDNA   [ Time Frame: After 24 weeks of treatment ]

7.  Secondary:   Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort   [ Time Frame: After 24 weeks of treatment ]

8.  Secondary:   Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort   [ Time Frame: After 24 weeks of treatment ]

9.  Secondary:   Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR   [ Time Frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) ]

10.  Secondary:   Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR   [ Time Frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days ) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) ]

11.  Secondary:   Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR   [ Time Frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) ]

12.  Secondary:   Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR   [ Time Frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) ]

13.  Secondary:   Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort   [ Time Frame: At the time of surgery (expected after 24 weeks of treatment) ]

14.  Secondary:   Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort   [ Time Frame: At the time of surgery (expected after 24 weeks of treatment) ]

15.  Secondary:   Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1   [ Time Frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days) ]

16.  Secondary:   Alpelisib PK Parameter: Cmax at Cycle 1 Day 1   [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days) ]

17.  Secondary:   Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1   [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days) ]

18.  Secondary:   Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1   [ Time Frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days) ]

19.  Secondary:   Alpelisib PK Parameter: Cmax at Cycle 4 Day 1   [ Time Frame: Cycle 4 Day 1 (each cycle is 28 days) ]

20.  Secondary:   Alpelisib PK Parameter: Tmax at Cycle 4 Day 1   [ Time Frame: Cycle 4 Day 1 (each cycle is 28 days) ]

21.  Secondary:   Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1   [ Time Frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days) ]

22.  Secondary:   Letrozole PK Parameter: Cmax at Cycle 1 Day 1   [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days) ]

23.  Secondary:   Letrozole PK Parameter: Tmax at Cycle 1 Day 1   [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days) ]

24.  Secondary:   Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1   [ Time Frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days) ]

25.  Secondary:   Letrozole PK Parameter: Cmax at Cycle 4 Day 1   [ Time Frame: Cycle 4 Day 1 (each cycle is 28 days) ]

26.  Secondary:   Letrozole PK Parameter: Tmax at Cycle 4 Day 1   [ Time Frame: Cycle 4 Day 1 (each cycle is 28 days) ]

27.  Secondary:   Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1   [ Time Frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days) ]

28.  Secondary:   Buparlisib PK Parameter: Cmax at Cycle 1 Day 1   [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days) ]

29.  Secondary:   Buparlisib PK Parameter: Tmax at Cycle 1 Day 1   [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days) ]

30.  Secondary:   Buparlisib PK Parameter: AUClast at Cycle 4 Day 1   [ Time Frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days) ]

31.  Secondary:   Buparlisb PK Parameter: Cmax at Cycle 4 Day 1   [ Time Frame: Cycle 4 Day 1 (each cycle is 28 days) ]

32.  Secondary:   Buparlisib PK Parameter: Tmax at Cycle 4 Day 1   [ Time Frame: Cycle 4 Day 1 (each cycle is 28 days) ]


  Serious Adverse Events


  Other Adverse Events


  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

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: novartis.email@novartis.com



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01923168     History of Changes
Other Study ID Numbers: CBYL719A2201
2013-001862-41 ( EudraCT Number )
First Submitted: August 13, 2013
First Posted: August 15, 2013
Results First Submitted: July 4, 2018
Results First Posted: September 14, 2018
Last Update Posted: September 14, 2018