Clinical trial NCT01495247: Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer
Official title: A Dose-finding Phase Ib Study Followed by an Open-label, Randomized Phase II Study of BEZ235 Plus Paclitaxel in Patients With HER2 Negative, Inoperable Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Inoperable Locally Advanced Breast Cancer
Metastatic Breast Cancer (MBC)
Keywords: Locally advanced
metastatic
breast cancer
HER2 negative
PI3K pathway
paclitaxel
mTOR inhibitor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-12-19
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a prospective, multi-center, open-label, phase Ib/ II study (two parts) with patients that have locally advanced or metastatic HER2 negative breast cancer. The first part (phase Ib) will investigate the MTD / Recommended Phase 2 Dose (RP2D) of the combination therapy of BEZ235 twice daily (b.i.d.) and weekly paclitaxel using a Bayesian model. When MTD/ RP2D is established the second part (phase II) will start. Phase II will evaluate the efficacy and the safety of weekly paclitaxel alone compared to weekly paclitaxel plus BEZ235 bid.


Eligibility criteria: Inclusion Criteria (phase lb):

* Females with Breast cancer that is histologically or cytologically confirmed, HER2 negative and locally advanced or metastatic as confirmed by radiology
* ECOG performance status 0 and 1
* Adequate bone marrow and organ function

Exclusion Criteria (Phase lb):

* Previous treatment with PI3K and/or mTOR inhibitors
* Symptomatic Central Nervous System (CNS) metastases
* Concurrent malignancy or malignancy in the last 5 years prior to start of study treatment
* Wide field radiotherapy ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug
* Active cardiac disease (e.g. LVEF less than institutional lower limit of normal, QTcF \> 480 msec, unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias)
* Inadequately controlled hypertension
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235 and/or paclitaxel
* Treatment at start of study treatment with drugs with a known risk to induce Torsades de Pointes, moderate and strong inhibitors or inducers of isoenzyme CYP3A4, warfarin and coumadin analogues, LHRH agonists
* Sensitivity to paclitaxel treatment
* Uncontrolled diabetes mellitus
* Pregnant or nursing (lactating) woman

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Phase lb: Dose Limiting Toxicities (DLTs) the first cycle of treatment
timeFrame: At first treatment intake (Cycle 1 Day 1 = C1D1), C1D8, C1D15, C1D22 and C2D1 [a cycle = 4 weeks = 28 days]
Secondary outcomes:
measure: Phase lb: Frequency and severity of adverse events
timeFrame: At screening, every week (C1D1, C1D8, C1D15, C1D22, C2D1, C2D8, etc.) until 30-45 days after treatment discontinuation [estimated time frame: 18 months].
measure: Phase lb: Progression free survival (PFS)
timeFrame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) until disease progression or death for any cause [estimated time frame: 18 months].
measure: Phase lb: Overall Response Rate (ORR)
timeFrame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months].
measure: Phase lb: Clinical Benefit Rate (CBR)
timeFrame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months].
Other outcomes:
Locations:
city: Dijon Cedex
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: