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Trial record 1 of 1 for:    NCT01572727
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A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation (BELLE-4)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01572727
First received: April 4, 2012
Last updated: January 27, 2017
Last verified: January 2017
  Purpose
This study evaluated whether the addition of daily BKM120 to weekly paclitaxel was effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer.

Condition Intervention Phase
Breast Cancer
Drug: Paclitaxel
Drug: BKM120 matching placebo
Drug: BKM120
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled, Phase II/III Study of BKM120 Plus Paclitaxel in Patients With HER2 Negative Inoperable Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Pathway Activation.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll) [ Time Frame: Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed ]
    PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.


Secondary Outcome Measures:
  • Overall Survival by Kaplan-Meier Estimate (Phase ll) [ Time Frame: every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed ]
    Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.

  • Overall Response Rate (Phase ll) [ Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment ]
    Percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. According to this criteria, CR = at least two determinations of CR at least 4 weeks apart before progression; PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  • Duration of Response (Phase Lll) [ Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment ]
    time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease

  • Time to Response (Phase Lll) [ Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment ]
    time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).

  • Clinical Benefit Rate (CBR) (Phase ll) [ Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment ]
    CBR was defined as the percentage of patients with an overall response of CR or PR or SD or non-CR/non-PD lasting more than 24 weeks based on local Investigator's assessment according to RECIST v1.1.

  • Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll) [ Time Frame: Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1. ]
    Summary statistics for PK: plasma concentration-time profiles of BKM120 and appropriate individual PK parameters based on population PK model , if deemed appropriate; each cycle = 28 days

  • Time to Definitive Deterioration of ECOG Performance Status (Phase Lll) [ Time Frame: every 4 weeks ]
    Time to definitive deterioration of the ECOG performance status from baseline


Enrollment: 416
Study Start Date: August 2012
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BKM120 and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.
Drug: Paclitaxel
intravenous paclitaxel 80 mg/m2 per week given until progression
Other Name: Taxol
Drug: BKM120
Buparlisib (BKM120) were supplied as 100 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.
Other Name: Buparlisib
Active Comparator: Placebo and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel.
Drug: Paclitaxel
intravenous paclitaxel 80 mg/m2 per week given until progression
Other Name: Taxol
Drug: BKM120 matching placebo

Buparlisib maching plaxcebo were supplied as 100 mg and 50 mg hard gelatin capsules.

Buparlisib placebo was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.


Detailed Description:
Based on the efficacy results at the time of the interim analyses, the DMC recommended stopping the study at Phase II during the interim as it met the protocol pre-specified futility criteria. Consequently, the Phase III portion of the study was not conducted.
  Eligibility

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

Inclusion Criteria:

  • Breast cancer that is locally advanced or metastatic
  • HER2 negative disease, and a known hormone receptor status - ER/PgR (common breast cancer classification tests)
  • A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
  • Adequate bone marrow and organ function
  • Measurable or non-measurable disease

Exclusion Criteria:

  • Prior chemotherapy for locally advanced or metastatic disease
  • Previous treatment with PI3K or AKT inhibitors
  • Patient has symptomatic CNS metastases
  • Concurrent malignancy or malignancy within 3 years of study enrollment
  • Hematopoietic colony-stimulating growth factors or radiation within 2-4 weeks prior to starting study drug
  • Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
  • Active heart (cardiac) disease as defined in the protocol
  • Known hypersensitivity or contraindications to use paclitaxel
  • Pregnant or nursing (lactating) woman
  • Certain scores on an anxiety and depression mood questionaire given at screening
  • Other protocol defined 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: NCT01572727

  Show 113 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01572727     History of Changes
Other Study ID Numbers: CBKM120F2202
2011-005932-24 ( EudraCT Number )
Study First Received: April 4, 2012
Results First Received: May 31, 2016
Last Updated: January 27, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
BKM120
paclitaxel
breast cancer
metastatic
locally advanced
PI3K
PIK3CA
PTEN

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017