Clinical Trials /

Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor

NCT01610284

Description:

The purpose of this study is to determine wether the addition of daily BKM120 to fulvestrant is effective and safe in treating patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer refractory to aromatase inhibitor.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor
  • Official Title: A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment

Clinical Trial IDs

  • ORG STUDY ID: CBKM120F2302
  • SECONDARY ID: 2011-005524-17
  • NCT ID: NCT01610284

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
BKM120 Matching placeboPlacebo and fulvestrant
FulvestrantBKM120 and fulvestrant
BKM120BKM120 and fulvestrant

Purpose

The purpose of this study is to determine wether the addition of daily BKM120 to fulvestrant is effective and safe in treating patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer refractory to aromatase inhibitor.

Trial Arms

NameTypeDescriptionInterventions
BKM120 and fulvestrantExperimentalBKM120 100mg given daily and fulvestrant 500mg given intramuscularly at cycle 1 day 1, cycle 1 day 15 and at day 1 at each cycle thereafter. Treatment will be given until disease progression or as described in the protocol
  • Fulvestrant
  • BKM120
Placebo and fulvestrantActive ComparatorBKM120 matching placebo given daily and fulvestrant 500mg given intramuscularly at cycle 1 day 1, cycle 1 day 15 and at day 1 at each cycle thereafter. Treatment will be given until disease progression or as described in the protocol
  • BKM120 Matching placebo
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  Locally advanced or metastatic breast cancer

          -  HER2-negative and hormone receptor-positive status (common breast cancer
             classification tests)

          -  Postmenopausal woman

          -  A tumor sample must be shipped to a Novartis designated laboratory for identification
             of biomarkers (PI3K activation status)

          -  Progression or recurrence of breast cancer while on or after aromatase inhibitor
             treatment

          -  Measurable disease or non measurable disease bone lesions in the absence of measurable
             disease as per RECIST 1.1

          -  Adequate bone marrow and organ function defined by laboratory values

        Exclusion Criteria:

          -  Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant

          -  More than one prior chemotherapy line for metastatic disease

          -  Symptomatic brain metastases

          -  Increasing or chronic treatment (> 5 days) with corticosteroids or another
             immunosuppressive agent

          -  Active heart (cardiac) disease as defined in the protocol

          -  Certain scores on an anxiety and depression mood questionnaires

          -  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:Progression free survival (PFS)
Time Frame:up to approx. 8.3 months
Safety Issue:
Description:PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomisation.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:up to approx. 32 months
Safety Issue:
Description:Time from date of randomization to the date of death from any cause. Patients will be followed up for the duration of the study and for an expected average of every 3 months after end of treatment.
Measure:Overall response rate (ORR)
Time Frame:up to approx. 8.3 months
Safety Issue:
Description:Proportion of patients with best overall response of complete response (CR) or partial response (PR) based according to RECIST 1.1.Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomisation.
Measure:Clinical benefit rate (CBR)
Time Frame:up to approx. 8.3 months
Safety Issue:
Description:Proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomisation.
Measure:Type, frequency and severity of adverse events
Time Frame:at minimum at each study visit and up to approx. 10 months
Safety Issue:
Description:Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
Measure:Plasma concentration of BKM120 and Fulvestrant (Pharmacokinetics)
Time Frame:Cycle 1 day 1, Cycle 1 day 15, cycle 2 day 1, cycle 2 day 2, cycle 2 day 15, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1 and cycle 6 day 1
Safety Issue:
Description:PK parameters; Patients will be assessed up to approx. 6 months after randomisation date. cycle = 28 days
Measure:Time profile of BKM120 and Fulvestrant (Pharmacokinetics)
Time Frame:Cycle 1 day 1, Cycle 1 day 15, cycle 2 day 1, cycle 2 day 2, cycle 2 day 15, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1 and cycle 6 day 1
Safety Issue:
Description:PK parameters; Patients will be assessed up to approx. 6 months after randomisation date. cycle = 28 days
Measure:Patient reported outcomes for global health status/QOL
Time Frame:Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment
Safety Issue:
Description:Time to definitive deterioration in global health status/QOL; Change from baseline in global health status/Quality of Life (QOL). Patients will be assessed up to approx. 8.3 months

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Breast cancer
  • Hormone receptor positive
  • HER2-negative
  • Metastatic
  • Locally advanced
  • PI3K
  • Fulvestrant
  • Refractory
  • Aromatase inhibitor

Last Updated

October 16, 2017