GINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer

Inclusion criteria

• Female ≥ 18 years
• ECOG ≤ 2
• Histologically confirmed endometrial cancer
• Not eligible for exclusive curative treatment by surgery and/or radiotherapy
• Initial metastatic endometrial cancer not treated with chemotherapy or radiotherapy prior to inclusion OR
• Recurrent endometrial cancer previously treated with adjuvant CT and RT, presenting with a disease-free interval of at least 12 months
• Presence of one or more measurable lesion(s) outside the irradiated areas
• Availability at inclusion of samples of tumor tissue (a block or at least 20 unstained slides) for tumor sub-classification and for routine molecular analysis
• Satisfactory biological functions: PNN ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, INR ≤ 2, standard normal values for potassium, calcium and magnesium, serum creatinine ≤ 1.5 x ULN or creatinine clearance > 50 mL/min, ALT and AST within normal range (or ≤ 3.0 x ULN if liver metastases present), Alkaline phosphatase ≤ 2.5 x ULN, serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome), fasting glycemia ≤ 120 mg/dL or ≤ 6.7 mmol/L
• Life expectancy 3 months
• Post menopausal woman with at least 12 months of natural (spontaneous) amenorrhea
• Negative serum pregnancy test ≤ 72 hours prior to initiating treatment for woman of child-bearing potential
• Consent form signed before any procedure performed

Exclusion criteria

• Previous treatment with PI3K inhibitors and/or mTOR
• Presence of symptomatic CNS metastases. Patient must have completed any prior treatment for CNS metastases ≥ 28 days and, if on corticosteroid therapy, should be receiving a stable low dose
• Concomitant presence or history of another malignant tumor in the past 3 years prior to inclusion (except spinocellular or cutaneous basal cell epithelioma or non-melanomatous skin cancer treated successfully)
• Suffering from mood disorders based on an evaluation by the investigator or a psychiatrist OR with a given score according to the PHQ-9 or GAD-7 mood evaluation scale (cf protocol)
• Concomitant administration of another approved or investigational anticancer agent
• Pelvic and/or para-aortic radiotherapy within ≤ 28 days prior to inclusion or persistent side effects from this treatment on implementation of the selection procedures
• Major surgery during the 28 days prior to starting investigational drug or persistent side effects from surgery
• Uncontrolled diabetes (HbA1c > 8 %)
• Presence of an active heart disease, especially: LVEF < 50 % determined by MUGA or ECHO, QTc > 480 msec on ECG recorded during selection (with QTcF formula), angina warranting the administration of anti-angina treatment, ventricular arrhythmia except for benign premature ventricular contractions, supraventricular and nodal arrhythmias warranting a pacemaker or not controlled by a treatment, conduction anomalies warranting a pacemaker, valvular disease with documented involvement of cardiac function, symptomatic pericarditis
• History of heart disease
• Currently receiving treatment to prolong QT interval accompanied by a known risk of triggering wave burst arrhythmia. Impossible to stop treatment or to replace it before starting study medication
• GI dysfunction or disease that could significantly interfere with absorption of BKM120
• Chronic treatment with corticosteroids or other immunosuppressants
• Any other severe and/or uncontrolled concomitant disease, which is likely to contraindicate the patient's participation
• Known treatment non-compliance
• Currently receiving treatment known to be inhibitors or moderate and strong inducers of isoenzyme CYP3A. Impossible to stop this treatment or to replace it with a different treatment before starting the study product
• Severe pneumonitis
• Grade ≥ 3 biological anomalies
• Known history of HIV infection
• Pregnant woman or nursing mother