Skip to main content
OpenTrials
Completed

NCT Number: NCT01572727

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral Nervous System Diseases Polyneuropathies Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Novartis Investigative Site, Sydney, New South Wales, Australia

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

paclitaxel

Drug

intravenous paclitaxel 80 mg/m2 per week given until progression

Other names: Taxol

BKM120 matching placebo

Drug

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.

BKM120

Drug

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 names: Buparlisib

Primary outcomes

  1. 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 outcomes

  1. 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.

  2. 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.

  3. 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

  4. 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).

  5. 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.

  6. 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

  7. 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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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.

Acronym: BELLE-4

Important dates

Study start
2012
Primary completion
2015
Study completion
2015
First posted
Apr 6, 2012
Registry last updated
Mar 9, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.