A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi (BELLE-3)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Metastatic Breast Cancer

Treatments: Drug: BKM120; Drug: Fulvestrant; Drug: BKM120 matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01633060

CBKM120F2303

2012-002571-34 (EudraCT Number)

Details and patient eligibility

About

This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment.

Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).

Full description

Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.

Enrollment: 432 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria

• Female patients age 18 years or older
• Histologically and/or cytologically confirmed diagnosis of breast cancer
• Radiologic evidence of inoperable locally advanced or metastatic breast cancer
• Adequate tumor tissue for the analysis of PI3K-related biomarkers
• Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive hormone receptor status
• Postmenopausal women
• Prior treatment with aromatase inhibitors
• Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry
• Adequate bone marrow and organ function
• ECOG performance status ≤ 2

Key exclusion criteria

• Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant
• More than one chemotherapy line for metastatic disease
• Hypersensitivity to any of the excipients of buparlisib or fulvestrant
• Symptomatic central nervous system metastases
• Concurrent malignancy or malignancy within 3 years of study enrollment
• Certain drugs or radiation within 2-4 weeks of enrollment
• Increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent
• Certain scores on an anxiety and depression mood questionnaire given at screening
• Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis C virus
• Active cardiac disease or a history of cardiac dysfunction

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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432 participants in 2 patient groups, including a placebo group

BKM120 100mg + Fulvestrant

Experimental group

Description:

BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.

Treatment:

Drug: BKM120

Drug: Fulvestrant

Placebo + Fulvestrant

Placebo Comparator group

Description:

BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.

Treatment:

Drug: BKM120 matching placebo

Drug: Fulvestrant