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Safety and Efficacy of BKM120 and Lapatinib in HER2+/PI3K-activated, Trastuzumab-resistant Advanced Breast Cancer

NCT01589861 · Status: TERMINATED · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2026-04-21

No results posted yet for this study

Summary

This study is based upon the following points:

1. Resistance to trastuzumab, either primary or secondary, is a clinically relevant issue.
2. PI3K/AKT activation, due to loss of expression/function of PTEN and/or activating mutations of PIK3CA, is a mechanism of resistance with clinical relevance in breast cancer. Such activation can be detected by:

* IHC evaluation of PTEN protein expression
* genotyping of PIK3CA exon 9 and 20
* IHC evaluation of phospho-AKT expression
3. BKM120 is an effective PI3K inhibitor. BKM120 and anti-HER2 therapy may have a synergistic antitumor activity in preclinical model of HER2+ breast cancer.
4. Lapatinib is an effective anti-HER2 therapy in trastuzumab-resistant disease.
5. For the evaluation of novel targeted therapies, selecting a patient population enriched for activation of the target to be modulated should allow to maximize the differences in clinical outcome that are expected in the experimental arm, and thus to minimize the patient number to include.
6. We propose to test in a phase I/II study the combination of lapatinib and BKM120 in trastuzumab-resistant HER2+ MBC patients, enriched for activation of PI3K/AKT as detected by loss of expression of PTEN (IHC), and/or mutation of PIK3CA and/or overexpression of phospho-AKT (IHC). Only for phase II patients, mutational status will be an inclusion criteria. For phase I patients molecular status will be a retrospective exploratory analysis.

Conditions

Interventions

DRUG

BKM120 + lapatinib

BKM120 40, 60 or 80 mg/day per os for 28 days cycle associated to lapatinib 750, 1000 or 1250 mg/day per os for 28 days cycle until progression or toxicity

Sponsors & Collaborators

  • Institut Paoli-Calmettes

    lead OTHER

Principal Investigators

  • Anthony GONCALVES, MD PhD · Institut Paoli-Calmettes

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2011-12-31
Primary Completion
2017-10-10
Completion
2017-10-10

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01589861 on ClinicalTrials.gov