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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: BKM120


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: stratum 1<br>Patients with low grade disease (grade 1 or 2) with positive or negative mutational status | Drug: BKM120<br>* per os, 60mg/j, until progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Efficacy | To determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety according to CTCAE v4.0 criteria and mood questionnaires : PHQ-9 and GAD-7 | To assess patient safety and the tolerance of BKM120 administered as monotherapy at the daily dose of 100 mg. | Patient will be followed for the duration of the study, an expected average of 75 days | 
| Efficacy: PFS | To evaluate progression-free survival | 6 months | 
| Efficacy: ORR | To evaluate the objective response rate according to RECIST 1.1 | Patient will be followed for the duration of the study, an expected average of 75 days | 
| Efficacy: overall survival | To evaluate overall survival. | Patients will be followed for an expected average of 1 year and 75 days | 
| Efficacy: duration of response | To evaluate the duration of the response. For patients in complete remission, the duration of the response will be calculated from the day on which a complete response is determined for the first time up to progression. For patients in partial remission, the duration of the response will be the overall response period calculated from the administration of the first treatment cycle up to the date of progression. | Patients will be followed for an expected average of 1 year and 75 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrial cancer, BKM, monotherapy, metastatic, initial treatment