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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01923168
First received: August 13, 2013
Last updated: July 27, 2017
Last verified: July 2017
  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

Condition Intervention Phase
Breast Cancer Drug: BYL719 Drug: BKM120 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 340
Actual Study Start Date: March 11, 2014
Study Completion Date: July 8, 2017
Primary Completion Date: July 8, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BYL719 + Letrozole
BYL719 + Letrozole in 120 patients
Drug: BYL719
BYL719 + Letrozole
Experimental: Buparlisib + Letrozole
Buparlisib + Letrozole in 120 patients
Drug: BKM120
BKM120 + Letrozole
Placebo Comparator: Placebo + Letrozole
Placebo (of Buparlisib or BYL719 ) with Letrozole in 120 patients
Drug: Placebo
Placebo (of BYL719 or BKM120) + Letrozole

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01923168

  Show 87 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01923168     History of Changes
Other Study ID Numbers: CBYL719A2201
Study First Received: August 13, 2013
Last Updated: July 27, 2017
Individual Participant Data (IPD) Sharing Statement:
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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Breast Cancer, Pathological Complete Response, neoadjuvant, hormone receptor-positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2017