GINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer
- Registration Number
- NCT01397877
- Lead Sponsor
- ARCAGY/ GINECO GROUP
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 24
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description stratum 1 BKM120 Patients with low grade disease (grade 1 or 2) with positive or negative mutational status
- Primary Outcome Measures
Name Time Method Clinical Efficacy 3 months To determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy.
- Secondary Outcome Measures
Name Time Method Efficacy: PFS 6 months To evaluate progression-free survival
Efficacy: ORR Patient will be followed for the duration of the study, an expected average of 75 days To evaluate the objective response rate according to RECIST 1.1
Safety according to CTCAE v4.0 criteria and mood questionnaires : PHQ-9 and GAD-7 Patient will be followed for the duration of the study, an expected average of 75 days To assess patient safety and the tolerance of BKM120 administered as monotherapy at the daily dose of 100 mg.
Efficacy: overall survival Patients will be followed for an expected average of 1 year and 75 days To evaluate overall survival.
Efficacy: duration of response Patients will be followed for an expected average of 1 year and 75 days 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.
Trial Locations
- Locations (45)
Institut Bergonié
🇫🇷Bordeaux, France
Hôpital Michallon - CHU Grenoble
🇫🇷Grenoble, France
Centre jean Bernard
🇫🇷Le Mans, France
Institut Ste Catherine
🇫🇷Avignon, France
Polyclinique Bordeaux Nord
🇫🇷Bordeaux, France
Centre jean Perrin
🇫🇷Clermont Ferrand, France
Centre Paul Papin
🇫🇷Angers, France
Centre Georges François leclerc
🇫🇷Dijon, France
Group Hospitalier Mutualiste de Grenoble
🇫🇷Grenoble, France
CHD Les Oudairies
🇫🇷la Roche sur Yon, France
Centre Hospitalier Régional
🇫🇷Orléans, France
Hôpital rené Huguenin
🇫🇷St Cloud, France
Centre Hospitalier de Blois
🇫🇷Blois, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Clinique Tivoli
🇫🇷Bordeaux, France
centre Francois baclesse
🇫🇷Caen, France
CHU Dupuytren
🇫🇷Limoges, France
CRLC Val d'Aurelle
🇫🇷Montpellier, France
Hôpital jean Minjoz
🇫🇷Besancon, France
Centre Oscar Lambret
🇫🇷Lille, France
Hôpital Prové Clairval
🇫🇷Marseille, France
Centre Catherine de Sienne
🇫🇷Nantes, France
ICO René Gauducheau
🇫🇷St Herblain, France
Centre Etienne DOLET
🇫🇷St Nazaire, France
Hôpitaux Civils de Colmar
🇫🇷Colmar, France
institut Paoli Calmette
🇫🇷Marseille, France
Groupement de coopération sanitaire
🇫🇷Montpellier, France
CHU Caremeau
🇫🇷Nimes, France
Clinique Bonnefon
🇫🇷Ales, France
Hôpital André Mignot
🇫🇷Le Chesnay, France
Centre Léon bérard
🇫🇷Lyon, France
Centre Alexis Vautrin
🇫🇷Nancy, France
Clinique Valdegour
🇫🇷Nimes, France
Centre d'oncologie de Gentilly
🇫🇷Nancy, France
Hopital Hotel Dieu
🇫🇷Paris, France
Centre Henri Becquerel
🇫🇷Rouen, France
Centre Eugene Marquis
🇫🇷Rennes, France
Clinique Armoricaine de Radiologie
🇫🇷Saint Brieuc, France
Hopital Tenon
🇫🇷Paris, France
Centre Frederic Joliot
🇫🇷Rouen, France
Institut cancérologuie de la loire
🇫🇷St Priest en Jarez, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Claudius Régaud
🇫🇷Toulouse, France
Hôpital Civil
🇫🇷Strasbourg, France
CHU Bretonneau
🇫🇷Tours, France