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

Novartis Pharmaceuticals416 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

416

Conditions

Breast Cancer

Interventions

PaclitaxelDRUG

intravenous paclitaxel 80 mg/m2 per week given until progression

BKM120 matching placeboDRUG

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.

BKM120DRUG

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.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (112)

Outcomes

Primary Outcomes

Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)

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.

Time frame: Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed

Secondary Outcomes

Overall Survival by Kaplan-Meier Estimate (Phase ll)

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.

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 Response Rate (Phase ll)

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.

Time frame: every 8 weeks after randomization Up to 3 months after end of Treatment

Duration of Response (Phase Lll)

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

Data from ClinicalTrials.gov

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