Safety and Efficacy of BKM120 and Lapatinib in HER2+/PI3K-activated, Trastuzumab-resistant Advanced Breast Cancer (PIKHER2)
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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)
- ≥ 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
Sites / Locations
- Institut Paoli-Calmettes
Arms of the Study
Arm 1
Experimental
BKM120+Lapatinib
BKM120 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