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

Phase 2 Multicenter Study to Assess the Safety and Efficacy of BKM120 as Monotherapy in Treatment of Initial or Recurrent Metastatic Endometrial Cancer After 1st Line Therapy in Patients Who Cannot Undergo Local Surgery and/or Radiotherapy

This study is to determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy.

Clinical efficacy will be determined by the non-progression rate at 3 or 2 months depending on the group of patients. The primary endpoint is the non-progression rate at 3 months (12 weeks) for the patient group whose disease is painless (low grade tumor = stratum 1) and the non-progression rate at 2 months (8 weeks) for the group of patients with an aggressive disease (high grade tumor = stratum 2).

Disease progression is defined by the RECIST 1.1 criteria

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