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Breast CancerPhase 1/2PIKHER2NCT01589861

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

A Phase 1/2 study testing BKM120 + lapatinib in people with Breast Cancer, run by Institut Paoli-Calmettes at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
BKM120 + lapatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteFrance
Study dates
Dec 2011to 10 Oct 2017
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female or male ≥ 18 years
  • WHO performance status ≤ 1
  • Locally advanced, recurrent or metastatic, histologically confirmed HER2 positive (IHC 3+ or FISH positive) breast cancer after failure of trastuzumab treatment.
  • while on trastuzumab or within 4 weeks since the last infusion of trastuzumab for metastatic disease within 12 months of the last infusion for patients who received trastuzumab as adjuvant or neoadjuvant treatment
  • For the phase II part, progression on trastuzumab must have occurred within 16 weeks before entering this trial.
  • should not have received more than 3 lines of anti-HER2 therapy.
Show all 13Show fewer
  • For the phase II part, activation of PI3K/AKT pathway
  • capable of understanding the protocol and has signed the informed consent
  • laboratory values within normal range
  • Measurable disease
  • Patients may have received treatment for brain metastases, but must be neurologically stable
  • Baseline LVEF>50% (MUGA or ECHO)
  • Affiliation to social security

Who cannot join

  • Previous treatment with lapatinib, neratinib or a PI3K inhibitor
  • untreated brain metastases.
  • acute or chronic liver, renal disease or pancreatitis
  • any peripheral neuropathy ≥ CTCAE grade 2
  • any of the following mood disorders, or meets the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9)
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
Show all 25Show fewer
  • ≥ CTCAE grade 3 anxiety
  • diarrhea ≥ CTCAE grade 2
  • active cardiac disease
  • history of cardiac dysfunction
  • poorly controlled diabetes mellitus (HbA1c > 8 %)
  • Other severe and/or uncontrolled concomitant medical conditions
  • Impairment of gastrointestinal function that may significantly alter the absorption of BKM120
  • been treated with any hematopoietic colony-stimulating growth factors ≤ 2 weeks prior to starting study drug.
  • currently receiving treatment with medication with a known risk prolong the QT interval or inducing Torsades de Pointes
  • currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A
  • receiving chronic treatment with steroids or another immunosuppressive agent.
  • have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies [other than trastuzumab] or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
  • have received small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy
  • have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • have undergone major surgery ≤ 28 days prior to starting study drug or who have not recovered from side effects of such therapy
  • Known diagnosis of HIV infection
  • History of another malignancy within 3 years
  • Patient is unable or unwilling to abide by the study protocol
  • pregnant or breast feeding women

Trial locations and contacts

1 site in 1 country.

France1 site

  • Institut Paoli-Calmettes

    Marseille, 13008

Other trials in France

About this study

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

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:
Read more
  • IHC evaluation of PTEN protein expression
  • genotyping of PIK3CA exon 9 and 20
  • IHC evaluation of phospho-AKT expression
  1. BKM120 is an effective PI3K inhibitor. BKM120 and anti-HER2 therapy may have a synergistic antitumor activity in preclinical model of HER2+ breast cancer.
  2. Lapatinib is an effective anti-HER2 therapy in trastuzumab-resistant disease.
  3. 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.
  4. 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
Being tested
BKM120 + lapatinib
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BKM120 + lapatinibDrug

    Also called BKM120 and 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

Study groups in NCT01589861
Study groupRoleWhat they receive
BKM120+LapatinibExperimentalBKM120 40, 60 or 80 mg/day per os for 28 days cycle + Lapatinib 750, 1000 or 1250 mg/day per os for 28 days cycle
Receives: Drug: BKM120 + lapatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase Ib: maximum-tolerated dose (MTD)

    To determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily lapatinib to adult patients trastuzumab-resistant HER2+ locally advanced, recurrent and metastatic breast cancer.

    Measured: Day 28

  2. Phase II: objective response rate (ORR)

    To determine the efficacy of daily BKM120 in combination with daily lapatinib as measured by objective response rate (ORR), defined by complete response (CR) or partial response (PR) of target and non target lesions according to RECIST V1.1., in patients with activation of PI3K/AKT pathway detected according to one at least of the following criteria, measured on primary or metastatic tissue: PTEN negative by IHC and/or somatic mutations (exons 9 and 20) of PIK3CA and/or Overexpression of phospho-AKT by IHC.

    Measured: until progression assessed up to 1 year

Secondary outcomes (4)

  1. safety

    Number of patients with adverse events (according to CTCAE V4)

    Measured: until progression or end of treatment assessed up to 1 year

  2. clinical benefit (CB)

    • To evaluate clinical benefit (CB defined as complete response (CR) + partial response (PR) + Stable disease (SD) > 6 months)

    Measured: until progression assessed up to 1 year

  3. progression-free survival (PFS)

    • To assess progression-free survival (PFS)

    Measured: until progression assessed up to 1 year

  4. pharmacokinetics

    • To determine pharmacokinetics profile (CMax, AUC) of oral BKM120 in combination with orally lapatinib and to monitor exposure to lapatinib

    Measured: D1, D8, D15, D22, D28 post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2012 (estimated)
  2. Study startDec 2011
  3. Primary completion10 Oct 2017
  4. Study completion10 Oct 2017

Why it stopped: Drug development withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01589861
Sponsor's protocol ID
PIKHER2/IPC 2011-001
Acronym
PIKHER2
Status last verified
Mar 2017
First submitted
28 Mar 2012
Last updated
21 Apr 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Guerin M, Rezai K, Isambert N, Campone M, Autret A, Pakradouni J, Provansal M, Camerlo J, Sabatier R, Bertucci F, Charafe-Jauffret E, Hervieu A, Extra JM, Viens P, Lokiec F, Boher JM, Goncalves A. PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer. Eur J Cancer. 2017 Nov;86:28-36. doi: 10.1016/j.ejca.2017.08.025. Epub 2017 Sep 23.

    PubMed 28950146

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BKM120 + lapatinib in people with Breast Cancer, run by Institut Paoli-Calmettes at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Drug development withdrawn). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ib: maximum-tolerated dose (MTD) (time frame: Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01589861, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.

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