Phase II, Open Label, Non-randomized, Trial of BKM120 as Palliative Treatment for Metastatic or Locally Advanced Cervical Cancer After Failure to Platinum Based Regimen
- Patient has provided a signed Informed Consent Form (ICF) obtained prior to any
- Female 18 years of age or older.
- Histologically or cytologically confirmed recurrent unresectable or metastatic cervix
- 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
- 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
- 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
- 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
- Known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
- 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)
- Obesity (exceeding the equipment limits)