Phase II, Open Label, Non-randomized, Trial of BKM120 for Metastatic or Locally Advanced Cervical Cancer

Inclusion Criteria:

* Patient has provided a signed Informed Consent Form (ICF) obtained prior to any screening procedure.
* Female 18 years of age or older.
* Histologically or cytologically confirmed recurrent unresectable or metastatic cervix squamous-cell carcinoma.
* ECOG performance status 0-2
* Adequate renal, hepatic and hematologic function:

  * ANC ≥1250/mm3;
  * Platelet count ≥100,000/mm3;
  * Hemoglobin ≥ 9.0 g/dL
  * Creatinine ≤1.5X upper limits of normal or 24 hrs clearance ≥55ml/min;
  * 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)
  * SGOT, SGPT ≤ 1.5 X upper limits of normal if no liver metastasis present;
  * SGOT, SGPT, alkaline phosphatase ≤ 3 X upper limits of normal if liver metastasis present;
* Measurable disease by magnetic resonance imaging according to RECIST criteria.
* Willingness and capacity in understand and comply with all of the trial planned procedures, including periodic medical visits, treatment plans and laboratory tests.
* Negative serum pregnancy test during screening and negative urinary test for pregnancy within 48 hours before starting study treatment in women with childbearing potential

Exclusion Criteria:

* Previous use of a PI3K inhibitor.
* Brain or spinal cord compressive metastasis. Patients with appropriately treated brain or spinal metastasis and neurologically stable for at least 4 weeks can be included at discretion of investigator.
* Concurrent malignancy other than non-melanoma skin cancer.
* Concurrent clinical condition impeditive to be part of the study at the judgment of the investigator.
* Patient has 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):

  * 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
* Patients with acute or chronic liver, renal disease or pancreatitis.
* Patients with diarrhea ≥ CTCAE grade 2.
* Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:

  * ST depression or elevation of ≥ 1.5 mm in 2 or more leads;
  * Congenital long QT syndrome;
  * History or presence of sustained ventricular arrhythmias or atrial fibrillation;
  * Clinically significant resting bradycardia (\< 50 beats per minutes);
  * QTc \> 480 msec on screening ECG;
  * Complete left bundle branch block;
  * Right bundle branch block + left anterior hemi block (bifascicular block) ;
  * Unstable angina pectoris ≤ 6 months prior to starting study drug;
  * Acute myocardial infarction ≤ 6 months prior to starting study drug;
  * Other clinically significant heart disease such as congestive heart failure requiring treatment (NYHA Class III or IV) or uncontrolled hypertension;
* Patients with clinical manifestation of diabetes mellitus (i.e. treated and/or with clinical signs) or steroid-induced diabetes mellitus or uncontrolled diabetes (Fasting glucose \>120 mg/dL (HbA1c \>8%).
* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
* 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).
* Patients who have received corticosteroids ≤ 2 weeks prior to starting study drug.
* Patient is currently being treated 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. Please refer to Table 5-8 for a list of prohibited CYP3A4 inhibitors and inducers.
* Employing an effective method of birth control. (Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months),
* must have a negative serum pregnancy test during screening and negative urinary test for pregnancy within 48 hours before starting study treatment in women with childbearing potential).
* Known diagnosis of human immunodeficiency virus (HIV) infection.
* Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator.
* Patient has received pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment in this study or has not recovered from side effects of such therapy at the time of initiation of screening procedures
* MRI study - additional exclusions to consider for an MRI study

  * Cardiac pacemaker
  * Ferromagnetic metal implants other than those approved as safe for use in MR scanners (Example: some types of aneurysm clips, schrapnel)
  * Claustrophobia
  * Obesity (exceeding the equipment limits)