NCT01589861

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

A Phase Ib/II Open-label Study Evaluating Safety and Efficacy of Oral BKM120 in Combination With Lapatinib in HER2+/PI3K-activated, Trastuzumab-resistant Locally Advanced, Recurrent and Metastatic Breast Cancer. PIKHER2/IPC 2011-001

• Status: Suspended
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 106 (estimated)
• Sponsor: Institut Paoli-Calmettes · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

• Breast Cancer

Interventions

Type	Name	Description
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

Timeline

• Start date: 2011-12-01
• Primary completion: 2018-01-01
• Completion: 2018-01-01
• First posted: 2012-05-02
• Last updated: 2017-03-28

Locations

1 site across 1 country: France