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 (BELLE-2)

Novartis

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01610284

2011-005524-17 (EudraCT Number)

CBKM120F2302

Details and patient eligibility

About

This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.

Full description

Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).

Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).

Enrollment: 1,147 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,147 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: Fulvestrant

Drug: BKM120

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