Clinical Trials /

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

NCT01923168

Description:

The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CBYL719A2201
  • NCT ID: NCT01923168

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
BYL719BYL719 + Letrozole
BKM120Buparlisib + Letrozole
PlaceboPlacebo + Letrozole

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
BYL719 + LetrozoleExperimentalBYL719 + Letrozole in 120 patients
  • BYL719
Buparlisib + LetrozoleExperimentalBuparlisib + Letrozole in 120 patients
  • BKM120
Placebo + LetrozolePlacebo ComparatorPlacebo (of Buparlisib or BYL719 ) with Letrozole in 120 patients
  • Placebo

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological Complete Response and Objective Response Rate
Time Frame:After 24 weeks of treatment
Safety Issue:
Description:Measure Pathological complete Response after 24 weeks of treatment and Objective response rate according to RECIST 1.1 after 24 weeks of treatment

Secondary Outcome Measures

Measure:Objective response rate according to RECIST 1.1 criteria
Time Frame:After 24 weeks of treatment
Safety Issue:
Description:pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment
Measure:Frequency and severity, of AEs and lab abnormalities
Time Frame:During 24 weeks of treatment
Safety Issue:
Description:To evaluate the safety and tolerability of study treatment based on the frequency, severity AEs, lab abnormalities
Measure:Rate breast conserving surgery
Time Frame:After 24 weeks of treatment
Safety Issue:
Description:Rate of breast conserving surgery, following completion of 24 weeks of treatment
Measure:Molecular markers and correlation with response
Time Frame:Baseline, Day 15 and 24 weeks of treatment
Safety Issue:
Description:Correlation between pCR and change in Ki67 from baseline to day 15 and baseline to surgery
Measure:PEPI (preoperative endocrine prognostic index) score
Time Frame:After 24 weeks of treatment
Safety Issue:
Description:To assess the Preoperative endocrine prognostic index (PEPI) score after 24 weeks of treatment
Measure: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
Safety Issue:
Description:Plasma concentration time profiles of BYL719/buparlisib and appropriate individual PK parameters Plasma concentration time profiles of letrozole and appropriate individual PK parameters

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Breast Cancer, Pathological Complete Response, neoadjuvant, hormone receptor-positive

Last Updated

July 27, 2017