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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01923168
Recruitment Status : Completed
First Posted : August 15, 2013
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

August 13, 2013
August 15, 2013
April 20, 2018
March 11, 2014
July 7, 2017   (Final data collection date for primary outcome measure)
Pathological Complete Response and Objective Response Rate [ Time Frame: After 24 weeks of treatment ]
Measure Pathological complete Response after 24 weeks of treatment and Objective response rate according to RECIST 1.1 after 24 weeks of treatment
Pathological Complete Response [ Time Frame: After 24 weeks of treatment ]
Measure Pathological complete Response after 24 weeks of treatment
Complete list of historical versions of study NCT01923168 on ClinicalTrials.gov Archive Site
  • Objective response rate according to RECIST 1.1 criteria [ Time Frame: After 24 weeks of treatment ]
    pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment
  • Frequency and severity, of AEs and lab abnormalities [ Time Frame: During 24 weeks of treatment ]
    To evaluate the safety and tolerability of study treatment based on the frequency, severity AEs, lab abnormalities
  • Rate breast conserving surgery [ Time Frame: After 24 weeks of treatment ]
    Rate of breast conserving surgery, following completion of 24 weeks of treatment
  • Molecular markers and correlation with response [ Time Frame: Baseline, Day 15 and 24 weeks of treatment ]
    Correlation between pCR and change in Ki67 from baseline to day 15 and baseline to surgery
  • PEPI (preoperative endocrine prognostic index) score [ Time Frame: After 24 weeks of treatment ]
    To assess the Preoperative endocrine prognostic index (PEPI) score after 24 weeks of treatment
  • Plasma concentration of BYL719/buparlisib and letrozole when given in combination [ Time Frame: Cycle 1 (Day 1, 2, 8, 15, 22), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4(Day 1 and Day 2), Cycle 5 Day 1 and Cycle 6 Day 1 ]
    Plasma concentration time profiles of BYL719/buparlisib and appropriate individual PK parameters Plasma concentration time profiles of letrozole and appropriate individual PK parameters
  • Objective response rate according to RECIST 1.1 criteria [ Time Frame: After 24 weeks of treatment ]
    Objective response rate according to RECIST 1.1 criteria after 24 weeks of treatment
  • Frequency and severity, of AEs and lab abnormalties [ Time Frame: During 24 weeks of treatment ]
    To evaluate the safety and tolerability of study treatment based on the frequency, severity AEs, lab abnormalities
  • Rate breast conserving surgery [ Time Frame: After 24 weeks of treatment ]
    Rate of breast conserving surgery, following completion of 24 weeks of treatment
  • Molecular markers and correlation with response [ Time Frame: Baseline, Day 15 and 24 weeks of treatment ]
    Correlation between pCR and change in Ki67 from baseline to day 15 and baseline to surgery
  • PEPI (preoperative endocrine prognostic index) score [ Time Frame: After 24 weeks of treatment ]
    To assess the Preoperative endocrine prognostic index (PEPI) score after 24 weeks of treatment
  • Plasma concentration of BYL719/buparlisib and letrozole when given in combination [ Time Frame: Cycle 1 (Day 1, 2, 8, 15, 22), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4(Day 1 and Day 2), Cycle 5 Day 1 and Cycle 6 Day 1 ]
    Plasma concentration time profiles of BYL719/buparlisib and appropriate individual PK parameters Plasma concentration time profiles of letrozole and appropriate individual PK parameters
Not Provided
Not Provided
 
Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
A Phase II Randomized, Double-blind Placebo Controlled, Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women With Hormone Receptor-positive HER2-negative Breast Cancer
The purpose of the study is to determine whether treatment with a PI3K inhibitor plus letrozole leads to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Breast Cancer
  • Drug: BYL719
    BYL719 + Letrozole
  • Drug: BKM120
    BKM120 + Letrozole
  • Drug: Placebo
    Placebo (of BYL719 or BKM120) + Letrozole
  • Experimental: BYL719 + Letrozole
    BYL719 + Letrozole in 120 patients
    Intervention: Drug: BYL719
  • Experimental: Buparlisib + Letrozole
    Buparlisib + Letrozole in 120 patients
    Intervention: Drug: BKM120
  • Placebo Comparator: Placebo + Letrozole
    Placebo (of Buparlisib or BYL719 ) with Letrozole in 120 patients
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
340
372
July 8, 2017
July 7, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patient is an adult, female ≥ 18 years old at the time of informed consent
  2. Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
  3. Patient is postmenopausal.
  4. Patient has T1c-T3, any N, M0, operable breast cancer
  5. Patients must have measurable disease
  6. Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
  7. Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
  8. Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing

Exclusion Criteria:

  1. Patient has locally recurrent or metastatic disease
  2. Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization.
  3. Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus
  4. History of acute pancreatitis within 1 year of study entry
  5. Uncontrolled hypertension
  6. Other protocol-defined inclusion/exclusion criteria may apply

Sexes Eligible for Study: Female
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Colombia,   Czechia,   Germany,   Hong Kong,   Israel,   Italy,   Japan,   Lebanon,   Netherlands,   Spain,   United States
Czech Republic,   France,   South Africa
 
NCT01923168
CBYL719A2201
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP