Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT01495247

Last Updated: 2020-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-30

Study Completion Date

2014-05-19

Brief Summary

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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.

Detailed Description

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Conditions

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Inoperable Locally Advanced Breast Cancer Metastatic Breast Cancer (MBC)

Keywords

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Locally advanced metastatic breast cancer HER2 negative PI3K pathway paclitaxel mTOR inhibitor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BEZ235 100 mg bid + paclitaxel 80 mg (phase lb)

Increasing doses of oral BEZ235 100 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days.

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

Doses of oral BEZ235 (BID), supplied as 50mg, 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion.

Paclitaxel

Intervention Type DRUG

The paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given.

BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts.

BEZ235 200 mg bid + paclitaxel 80 mg (phase lb)

Increasing doses of oral BEZ235 200 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

Doses of oral BEZ235 (BID), supplied as 50mg, 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion.

Paclitaxel

Intervention Type DRUG

The paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given.

BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts.

Interventions

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BEZ235

Doses of oral BEZ235 (BID), supplied as 50mg, 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion.

Intervention Type DRUG

Paclitaxel

The paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given.

BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Dijon, , France

Site Status

Novartis Investigative Site

Saint-Herblain Cédex, , France

Site Status

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Site Status

Countries

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Brazil United States France Spain

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13703

Results for CBEZ235B2101 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

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2011-002400-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBEZ235B2101

Identifier Type: -

Identifier Source: org_study_id