Ignite Creation Date:
2025-12-24 @ 12:44 PM
Ignite Modification Date:
2025-12-28 @ 4:52 AM
Study NCT ID:
NCT01589861
Status:
SUSPENDED
Last Update Posted:
2017-03-28
First Post:
2012-03-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of BKM120 and Lapatinib in HER2+/PI3K-activated, Trastuzumab-resistant Advanced Breast Cancer
Sponsor:
Institut Paoli-Calmettes
Organization:
Study Overview
Official Title:
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
Status Verified Date:
2017-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Data analysis
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PIKHER2
Brief 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.
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.
Detailed Description:
None
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: