<br>        Inclusion Criteria:<br><br>          1. Male or female adult patients (> 18 years)<br><br>          2. Patients with histologically/cytologically confirmed diagnosis of the following<br>             advanced tumors that have progressed despite standard therapy or that have no<br>             available established treatments: metastatic breast cancer, pancreatic<br>             adenocarcinoma, metastatic CRC or recurrent GBM will be included.<br><br>          3. Provision of an archival tumor sample to a Novartis designated laboratory for<br>             molecular profiling. The tumor material submitted for these analyses may have been<br>             obtained at any time during the course of the patient's disease.<br><br>          4. Measurable disease as assessed by RECIST 1.1 for non-GBM tumors and by RANO criteria<br>             for GBM.<br><br>          5. ECOG (WHO) performance status 0-2<br><br>          6. Adequate bone marrow and organ function<br><br>          7. Patient is able to swallow and retain oral medication<br><br>          8. Negative serum pregnancy test; non-lactating or post-menopausal women.<br><br>        Exclusion Criteria:<br><br>        1.Use of other investigational drugs within 30 days of enrollment or 5 half-lives of<br>        enrollment, whichever is longer. 2.History of hypersensitivity to LDE225, BKM120 or to<br>        drugs of similar chemical classes.<br><br>        3.Patient has received previous treatment with PI3K inhibitors and/or smoothened<br>        inhibitors.<br><br>        4.Patients with recurrent GBM who have received radiotherapy within 3 months of initiating<br>        study treatment.<br><br>        5.Patients with primary CNS tumor (except recurrent GBM), uncontrolled or symptomatic CNS<br>        metastasis. However, patients with controlled, asymptomatic or with resected CNS<br>        metastases with no radiological evidence of disease or with stable brain metastasis with<br>        no progression may be are eligible.<br><br>        6.Patients who have neuromuscular disorders or are on concomitant treatment with drugs<br>        that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins),<br>        clofibrate and gemfibrozil. If it is essential that the patient remains on a statin to<br>        control hyperlipidemia, only Pravastatin may be used with extra caution.<br><br>        7.Patients who require the use of warfarin (substrate of CYP2C9) cannot be enrolled as<br>        LDE225 and BKM120 are competitive inhibitors of CYP2C9 based on in-vitro data.<br><br>        8.Patient is currently being treated with drugs known to be strong inhibitors or inducers<br>        of CYP3A4/5, which cannot be discontinued or switched to a different medication 7 days<br>        prior to starting study treatment and for the duration of the study.<br><br>        9.Patient has a score =12 on the PHQ-9 questionnaire. A normal evaluation by a<br>        psychiatrist or psychologist can overrule this exclusion).<br><br>        10.Patients who select responses of 1, 2 or 3 to question number 9 on the PHQ-9<br>        questionnaire regarding potential for suicidal thoughts or ideation (independent of the<br>        total score of the PHQ-9), (a normal evaluation by a psychiatrist or psychologist can<br>        overrule this exclusion).<br><br>        11.Patient has a GAD-7 mood scale score = 15, (a normal evaluation by a psychiatrist or<br>        psychologist can overrule this exclusion) 12.Patient has a documented medical history of<br>        or active major depression episode, bipolar disorder (I or II), obsessive compulsive<br>        disorder, schizophrenia, a history of suicidal attempts or ideation, or homicidal ideation<br>        (e.g. risk of doing harm to self or others) 13. Patient has =CTCAE grade 3 anxiety<br>        14.Current medical history of the following:<br><br>          -  Use of a pacemaker<br><br>          -  History of or presence of clinically significant ventricular or atrial<br>             tachyarrhythmia<br><br>          -  Clinically significant resting bradycardia (< 45 beats per minute)<br><br>          -  History of clinically documented myocardial infarction<br><br>          -  History of unstable angina pectoris<br><br>          -  History of known structural abnormalities (i.e. cardiomyopathy) 15.Clinically<br>             significant cardio-vascular disease 16.Clinically significant abnormal ECG 17.Left<br>             Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated Acquisition<br>             (MUGA) scan or echocardiogram (ECHO) 18.Patient is currently receiving treatment with<br>             QT prolonging medication known to have a risk to induce Torsades de Pointes, and the<br>             treatment cannot be discontinued or switched to a different medication 7 days prior<br>             to starting the study and for the duration of the study 19.Patients who are not<br>             willing to apply highly effective contraception as defined by the protocol during the<br>             study and through the duration of the study. Note: Hormonal contraception methods<br>             (e.g. oral, injected, implanted) are not allowed as it cannot be ruled out that the<br>             study drug decreases the effectiveness of hormonal contraception 20.Sexually active<br>             males who are unwilling to use a condom during intercourse while taking drug and for<br>             6 months after stopping investigational medications and agree not father a child in<br>             this period.<br><br>             21.Patients is currently receiving increasing or chronic treatment with<br>             corticosteroids ((= the anti-inflammatory potency of 4mg dexamethasone) or another<br>             immunosuppressive agent.<br><br>             22.Patient has been treated with any hematopoietic colony-stimulating growth factors<br>             (e.g., G-CSF, GM-CSF) = 2 weeks prior to starting study drug. Erythropoietin or<br>             darbepoetin therapy, if initiated before enrollment, may be continued 23.Patient who<br>             has received chemotherapy, targeted therapy or immunotherapy = 3 weeks (6 weeks for<br>             nitrosourea, mitomycin-C or monoclonal antibodies; 1 week for hormonal anti-cancer<br>             therapy) prior to starting study drug or who have not recovered to grade 1 or better<br>             from related side effects of such therapy (exceptions include alopecia, bone marrow<br>             and organ functions) 24.Patient has impairment of gastrointestinal (GI) function or<br>             GI disease that may significantly alter the absorption of LDE225 and BKM120 (e.g.,<br>             ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,<br>             or small bowel resection) 25.Patient has a known history of HIV infection (testing<br>             not mandatory)<br><br>        AMENDMENT 1 CHANGES:<br><br>        Inclusion Criteria:<br><br>        3. Provision of an archival tumor sample to a Novartis designated laboratory for molecular<br>        profiling. It is accepted that it may not be possible to obtain all samples prior to<br>        commencing study treatment. It is also accepted that it may not be possible to obtain a<br>        sample (e.g. if sufficient sample does not exist), and in this situation inclusion of the<br>        patient should be discussed with Novartis (as this may not make a patient ineligible).<br><br>        Exclusion Criteria:<br><br>        5. Patients with primary CNS tumor (except recurrent GBM), uncontrolled or symptomatic CNS<br>        metastasis. However, patients with controlled, asymptomatic or with resected CNS<br>        metastases with no radiological evidence of disease or with stab