Know Cancer

or
forgot password

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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer

Thank you

Trial Information

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


Inclusion Criteria:



1. Female or male ≥ 18 years

2. WHO performance status ≤ 1

3. 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

4. For the phase II part, progression on trastuzumab must have occurred within 16 weeks
before entering this trial.

5. should not have received more than 3 lines of anti-HER2 therapy.

6. For the phase II part, activation of PI3K/AKT pathway

7. capable of understanding the protocol and has signed the informed consent

8. laboratory values within normal range

9. Measurable disease

10. Patients may have received treatment for brain metastases, but must be neurologically
stable

11. Baseline LVEF>50% (MUGA or ECHO)

12. Affiliation to social security

Exclusion Criteria:

1. Previous treatment with lapatinib, neratinib or a PI3K inhibitor

2. untreated brain metastases.

3. acute or chronic liver, renal disease or pancreatitis

4. any peripheral neuropathy ≥ CTCAE grade 2

5. 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

6. diarrhea ≥ CTCAE grade 2

7. active cardiac disease

8. history of cardiac dysfunction

9. poorly controlled diabetes mellitus (HbA1c > 8 %)

10. Other severe and/or uncontrolled concomitant medical conditions

11. Impairment of gastrointestinal function that may significantly alter the absorption
of BKM120

12. been treated with any hematopoietic colony-stimulating growth factors ≤ 2 weeks prior
to starting study drug.

13. currently receiving treatment with medication with a known risk prolong the QT
interval or inducing Torsades de Pointes

14. currently being treated with drugs known to be moderate and strong inhibitors or
inducers of isoenzyme CYP3A

15. receiving chronic treatment with steroids or another immunosuppressive agent.

16. 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

17. 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

18. 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

19. have undergone major surgery ≤ 28 days prior to starting study drug or who have not
recovered from side effects of such therapy

20. Known diagnosis of HIV infection

21. History of another malignancy within 3 years

22. Patient is unable or unwilling to abide by the study protocol

23. pregnant or breast feeding women

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase Ib: maximum-tolerated dose (MTD)

Outcome Description:

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.

Outcome Time Frame:

Day 28

Safety Issue:

Yes

Principal Investigator

Anthony GONCALVES, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Institut Paoli-Calmettes

Authority:

France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:

PIKHER2/IPC 2011-001

NCT ID:

NCT01589861

Start Date:

December 2011

Completion Date:

September 2014

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms

Name

Location