A Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: BKM120
Intervention description: BKM120 oral capsules. 100 mg daily in cycles of 28 days, until disease progression
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: breast cancer; metastatic; triple negative breast cancer; BKM120; SOLTI; PI3K inhibitor

Summary:

      The purpose of this study is to evaluate the clinical activity of BKM120 in patients with
      metastatic triple-negative breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically and radiologically confirmed metastatic TNBC (Stage IV disease),
             previously documented by histological analysis, which is ER-negative and PR-negative
             by IHC and HER2 negative by IHC or FISH/CISH.

          -  Subjects must have received maximum two prior chemotherapy regimens for metastatic
             breast cancer.

          -  Availability of a representative tumor specimen (primary or metastasis, archival
             tissue or fresh biopsy for patients with biopsiable tumor) at baseline.

          -  At least one measurable lesion by RECIST 1.1

          -  Age ≥ 18 years at the day of consenting to the study

          -  ECOG performance status ≤ 2

          -  Adequate bone marrow and organ function as defined by the following laboratory values:
             ANC ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, INR ≤ 2; serum
             potassium between 3.0mmol/L and 5.5 mmol/L; Corrected serum calcium between8.0mg/dL
             and 11.5mg/dL (OR between 1.0mmol/L and 1.5mmol/L of Ionized calcium); serum magnesium
             between 1.2mg/dL and 3.0 mg/dL; serum creatinine ≤ 1.5 x ULN, ALT and AST within
             normal range (or ≤ 3.0 x ULN if liver metastases are present); serum bilirubin within
             normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0
             x ULN with direct bilirubin within normal range in patients with well documented
             Gilbert Syndrome); fasting plasma glucose (FPG) ≤ 140 mg/dL or ≤ 7.8 mmol/L.

        Exclusion Criteria:

          -  Previous treatment with PI3K inhibitors

          -  Symptomatic CNS metastases

          -  Patients with controlled and asymptomatic CNS metastases may participate in this
             trial. As such, the patient must have completed any prior treatment for CNS metastases
             > 28 days (including radiotherapy and/or surgery) prior to enrollment in this study.
             Patients with previously treated brain metastases, who are on a stable low dose
             corticosteroids treatment are eligible

          -  Concurrent malignancy or malignancy within 3 years of study enrollment (with the
             exception of adequately treated basal or squamous cell carcinoma or non-melanomatous
             skin cancer). An exception to this rule are those patients with documented germline
             mutations in BRCA1 or 2, who may have previous history of cancer

          -  Any of the following mood disorders as judged by the Investigator or a Psychiatrist,
             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)

               1. Patients with a history or active episodes of major depression, bipolar disorder
                  (I or II), obsessive-compulsive disorder, schizophrenia, history of suicide
                  attempts or suicidal thoughts (eg. Risk of hurting or harming others) or patients
                  with severe personality disorders (as defined by the DSM-IV) are not eligible.
                  Note: For patients who are treated with psychotropic drugs at baseline, the dose
                  and schedule shall not be changed during the 6 weeks prior to initiation of
                  treatment with the study drug.

               2. ≥ CTCAE v 4.0 grade 3 anxiety

          -  Patients on concurrent use of other approved or investigational antineoplastic and /
             or chemotherapy or any continuous or intermittent treatment with therapeutic agents of
             low molecular weight (excluding monoclonal antibodies) in ≤ 21 days prior to
             enrollment in this study or who have not recovered from the effects such therapy will
             not be eligible.

          -  Radiotherapy ≤ 28 days prior to enrollment in this study or failure to recover from
             side effects of such therapy at the time of initiation of screening procedures.

          -  Major surgery within 28 days prior to starting study drug or has not recovered from
             major side effects of the surgery

          -  Poorly controlled diabetes mellitus (HbA1c > 8%)

          -  Active cardiac disease including any of the following:

               1. Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated
                  acquisition (MUGA) scan or echocardiogram (ECHO)Note: ECHO/MUGA is only required
                  at baseline if patient has a history of abnormal cardiac test results

               2. QTc > 480 msec on screening ECG (using the QTcF formula

               3. Angina pectoris that requires the use of anti-anginal medication

               4. Ventricular arrhythmias except for benign premature ventricular contractions

               5. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
                  with medication

               6. Conduction abnormality requiring a pacemaker

               7. Valvular disease with documented compromise in cardiac function

               8. Symptomatic pericarditis

          -  History of cardiac dysfunction including any of the following;

               1. Myocardial infarction within the last 6 months, documented by persistent elevated
                  cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF
                  function

               2. History of documented congestive heart failure (New York Heart Association
                  functional classification III-IV)

               3. Documented cardiomyopathy

          -  Treatment with QT prolonging medication known to have a risk to induce Torsades de
             Pointes, and the treatment cannot be discontinued or switched to a different
             medication prior to starting study drug

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of BKM120 (e.g., uncontrolled nausea, vomiting, diarrhea,
             malabsorption syndrome, or small bowel resection)

          -  Chronic treatment with steroids or another immunosuppressive agent. Note: Topical
             applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye
             drops or local injections (e.g., intra-articular) are allowed. Patients with
             previously treated brain metastases, who are on a stable low dose corticosteroids
             treatment (e.g., dexamethasone 2 mg/day, prednisone 10 mg/day) for at least 14 days
             before start of study treatment, are eligible

          -  Other concurrent severe and/or uncontrolled medical condition that would, in the
             investigator's judgment contraindicate her participation in the clinical study (e.g.,
             chronic pancreatitis, active chronic hepatitis etc.)

          -  History of non-compliance to medical regimen

          -  Current treatment with drugs known to be moderate and strong inhibitors or inducers of
             isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different
             medication prior to starting study drug

          -  Known history of HIV (testing not mandatory) infection

          -  Pregnant or nursing (lactating) woman

          -  Woman of child-bearing potential unwilling to observe total sexual abstinence or to
             use a double barrier method for birth control throughout the trial. Reliable
             contraception should be maintained throughout the study and for 6 months after study
             drug discontinuation