BKM120 in Metastatic Castration-resistant Prostate Cancer
Condition: Prostate Cancer; Metastatic (Spread to Other Areas of the Body)
MeSH terms: Prostatic Neoplasms
Intervention: BKM120
Intervention description: BKM120 at the maximum tolerated dose (MTD) of 100mg orally daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BKM120; prostate cancer; metastatic castrate-resistant prostate cancer (mCRPC)

Summary:

      The purpose of this study is to evaluate the effects of the study drug, BKM120. The study
      drug, BKM120, is an inhibitor of a protein called phosphatidyl inositol-3-kinase (PI3K). This
      protein is found in normal cells and in cancer cells, but often in many cancer cells this
      protein is overactive. Inhibiting the protein may slow the growth of prostate cancer but this
      has not been tested yet in men with prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Karnofsky performance status ≥ 70

          -  Life expectancy of ≥ 12 weeks as determined by treating investigator

          -  Adequate laboratory parameters

          -  Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic
             variants of prostate cancer, including neuroendocrine features and small cell
             carcinoma of the prostate are permitted

          -  Radiographic evidence of metastatic disease

          -  Evidence of disease progression on androgen deprivation therapy (ADT)

          -  A minimum of 4 weeks elapsed off of antiandrogen therapy prior to registration (i.e.
             flutamide, nilutamide) and 6 weeks for bicalutamide, without evidence of an
             anti-androgen withdrawal response. Patients who did not have a PSA decline with the
             most recent antiandrogen therapy require only a 2 week washout period prior to
             registration

          -  A minimum of 2 weeks from prior abiraterone acetate, sipuleucel-T, MDV3100, orteronel
             (TAK700), ketoconazole, or other experimental anti-cancer therapies prior to
             registration is required. Concomitant treatment with enzalutamide is permitted.

          -  At least one prior systemic chemotherapy regimen FDA approved for metastatic prostate
             cancer

          -  A minimum of 4 weeks from any major surgery prior to registration

        Exclusion Criteria:

          -  Have received prior treatment with a PI3K inhibitor

          -  Known hypersensitivity to BKM120 or to its excipients

          -  Untreated brain metastases

          -  Patients with hepatitis B or C, other acute or chronic liver disease, or a recent
             (within 12 months of administration of first dose of study drug) history of
             pancreatitis

          -  Patients with certain mood disorders as judged by the investigator or a psychiatrist

          -  History of treatment in an inpatient psychiatric setting

          -  Concurrent severe and/or uncontrolled cardiac conditions which could compromise
             participation in the study

          -  Other concurrent severe and/or uncontrolled concomitant medical conditions that could
             cause unacceptable safety risks or compromise compliance with the protocol

          -  Uncontrolled diabetes mellitus defined as a fasting plasma glucose level of >120.

          -  Diarrhea ≥ CTCAE grade 2

          -  Drugs or substances known to be strong inhibitors or inducers of the isoenzyme CYP3A4
             should be avoided as systemic therapy in association with BKM120 as these can alter
             its metabolism. Topical use of creams or other applications not absorbed into the
             circulation is permitted

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

          -  Have been treated with any granulocyte colony-stimulating growth factors (e.g., G-CSF,
             GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy,
             if initiated at least 2 weeks prior to enrollment, may be continued

          -  Currently receiving treatment with medication that has the potential to significantly
             prolong the QT interval or induce Torsades de Pointes, and the treatment cannot either
             be discontinued or switched to a different medication prior to starting study drug

          -  Have received immunosuppressive therapy including corticosteroids ≤ 2 weeks prior to
             starting study drug. Prednisone at a total daily dose of 10 mg orally or its
             equivalent is permitted, if initiated at least 2 weeks prior to enrollment

          -  History of solid organ or stem cell transplantation

          -  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 prior to administration of first dose of study drug

          -  Have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not
             recovered from side effects of such therapy prior to administration of first dose of
             study drug

          -  Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative
             anticoagulant

          -  Known diagnosis of human immunodeficiency virus (HIV) infection

          -  History of another malignancy within 3 years, except cured basal cell or squamous cell
             carcinoma of the skin or low grade papillary bladder cancer Other inclusion and
             exclusion criteria apply