initial or recurrent metastatic endometrial cancer after first line therapy in patients who cannot undergo local surgery and/or radiotherapy.
Conditions
Interventions
Product Code: BKM120
Pharmaceutical Form: Capsule
Sponsors
ARCAGY
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Female = 18 years old. • ECOG performance index 0-2. • Patient with histological confirmed endometrial cancer. • Patient who is not eligible for exclusive curative treatment by surgery and/or radiotherapy. • Patient with initial metastatic endometrial cancer that has not been treated with chemotherapy or radiotherapy prior to inclusion OR Patient with recurrent endometrial cancer previously treated with adjuvant chemotherapy and radiotherapy, presenting with a disease-free interval (period between the date of the last dose of chemotherapy and relapse) of at least 12 months. • Presence of one or more measurable lesion(s) outside the irradiated areas. • Availability at the time of inclusion of samples of tumor tissue, in the form of archived tissue (a block or at least 20 unstained slides) for tumor sub-classification (low grade = stratum 1; high grade = stratum 2) and for routine molecular analysis. • Satisfactory biological functions • Life expectancy 3 months. • The Information Consent Form (ICF) must be signed by the patient before any procedure is carried out. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 56 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Previous treatment with PI3K inhibitors and/or mTOR. • Presence of symptomatic central nervous system (CNS) metastases. • Concomitant presence or history of another malignant tumor in the past 3 years prior to inclusion in the study (with the exception of spinocellular or cutaneous basal cell epithelioma or non-melanomatous skin cancer treated successfully). • Patient suffering from one of the following mood disorders based on an evaluation by the investigator or a psychiatrist OR with a limit score of = 10 on the PHQ-9 (Patient Health Questionnaire) OR a limit score of = 15 on the GAD-7 mood evaluation scale, respectively, OR with a positive response of "1, 2, or 3" to question number 9 relating to suicidal ideation in the PHQ-9 questionnaire (regardless of the overall score obtained in PHQ-9). o Medically documented earlier or active major depressive episodes, bipolar disorders (I or II), compulsive obsessive disorders, schizophrenia, history of suicide attempts or suicidal ideation or homicidal ideation (immediate risk of harming another person). o Anxiety = grade 3 CTCAE • Concomitant administration of another approved or investigational anticancer agent (hormonal agents included). • Pelvic and/or para-aortic radiotherapy within = 28 days prior to inclusion in the study or persistent side effects from this treatment on implementation of the selection procedures. • Major surgery during the 28 days prior to starting the investigational drug or persistent side effects from surgery. • Uncontrolled diabetes (HbA1c > 8 %). • Presence of an active heart disease • History of heart disease • Currently receiving treatment to prolong the QT interval accompanied by a known risk of triggering wave burst arrhythmia. • Gastrointestinal dysfunction (GI) or gastrointestinal disease (GD) that could significantly interfere with absorption of BKM120. • Chronic treatment with corticosteroids or other immunosuppressants. • Any other severe and/or uncontrolled concomitant disease • Currently receiving treatment known to be inhibitors or moderate and strong inducers of isoenzyme CYP3A. • Severe pneumonitis. • Grade = 3 biological anomalies. • Known history of HIV infection. • Pregnant woman or nursing mother • Woman of child-bearing potential must use highly effective contraception and must have a negative serum pregnancy test = 72 hours prior to initiating treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemiotherapy. 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).;Secondary Objective: • safety and tolerance • progression-free survival at 6 months • objective response rate • duration of response. • overall survival. • mutational status of PIK3CA, PIK3R1, KRAS, BRAF, ß-catenine, AKT and PTEN genes on archived tumor block. • PTEN, AKT, TSC2, EUH, LE PR, pS6, pAKT, HER2 and LKB1 gene expression on archived tumor block. • amplified genes (including, for example: PIK3CA, PIK3CB, PTEN, TSC2, AKT, LKB1 genes) on archived tumor block • changes in biomarkers (e.g. p-AKT, p-S6, p-4EBP1) before and after treatment on recent tumor biopsies (if available). • To correlate the molecular anomalies observed and the efficacy of BKM120.;Primary end point(s): Non-progression rate according to RECIST 1.1 ;Timepoint(s) of evaluation of this end point: at 3 (stratum 1) or 2 months (stratum 2) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Safety according to CTCAE v4.0 criteria and mood questionnaires : PHQ-9 and GAD-7 -PFS at 6 months -ORR according to RECIST 1.1 -Duration of response -Overall Survival - Exploratory;Timepoint(s) of evaluation of this end point: during all the time of the study | — |
Countries
France
Contacts
Public ContactSponsor office
ARCAGY
Outcome results
None listed