Clinical trial NCT01397877: GINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: endometrial cancer
BKM
monotherapy
metastatic
initial treatment
Lead sponsor: ARCAGY/ GINECO GROUP
Sponsor class: OTHER
First posted: 2011-07-20
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Clinical Efficacy
timeFrame: 3 months
Secondary outcomes:
measure: Safety according to CTCAE v4.0 criteria and mood questionnaires : PHQ-9 and GAD-7
timeFrame: Patient will be followed for the duration of the study, an expected average of 75 days
measure: Efficacy: PFS
timeFrame: 6 months
measure: Efficacy: ORR
timeFrame: Patient will be followed for the duration of the study, an expected average of 75 days
measure: Efficacy: overall survival
timeFrame: Patients will be followed for an expected average of 1 year and 75 days
measure: Efficacy: duration of response
timeFrame: Patients will be followed for an expected average of 1 year and 75 days
Other outcomes:
Locations:
city: Ales
country: France
facility: Clinique Bonnefon
city: Angers
country: France
facility: Centre Paul Papin
city: Avignon
country: France
facility: Institut Ste Catherine
city: Besancon
country: France
facility: Hôpital jean Minjoz
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Caen
country: France
facility: centre Francois baclesse
city: Clermont Ferrand
country: France
facility: Centre jean Perrin
city: Colmar
country: France
facility: Hôpitaux Civils de Colmar
city: Dijon
country: France
facility: Centre Georges François leclerc
city: Grenoble
country: France
facility: Group Hospitalier Mutualiste de Grenoble
city: Grenoble
country: France
facility: Hôpital Michallon - CHU Grenoble
city: la Roche sur Yon
country: France
facility: CHD Les Oudairies
city: Le Chesnay
country: France
facility: Hôpital André Mignot
city: Le Mans
country: France
facility: Centre jean Bernard
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Centre Léon bérard
city: Marseille
country: France
facility: Hôpital Prové Clairval
city: Marseille
country: France
facility: institut Paoli Calmette
city: Montpellier
country: France
facility: CRLC Val d'Aurelle
city: Montpellier
country: France
facility: Groupement de coopération sanitaire
city: Nancy
country: France
facility: Centre Alexis Vautrin
city: Nancy
country: France
facility: Centre d'oncologie de Gentilly
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nimes
country: France
facility: CHU Caremeau
city: Nimes
country: France
facility: Clinique Valdegour
city: Orléans
country: France
facility: Centre Hospitalier Régional
city: Paris
country: France
facility: Hopital Hotel Dieu
city: Paris
country: France
facility: Hopital Tenon
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Frederic Joliot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Brieuc
country: France
facility: Clinique Armoricaine de Radiologie
city: St Cloud
country: France
facility: Hôpital rené Huguenin
city: St Herblain
country: France
facility: ICO René Gauducheau
city: St Nazaire
country: France
facility: Centre Etienne DOLET
city: St Priest en Jarez
country: France
facility: Institut cancérologuie de la loire
city: Strasbourg
country: France
facility: Hôpital Civil
city: Toulouse
country: France
facility: Centre Claudius Régaud
city: Tours
country: France
facility: CHU Bretonneau
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: GINECO - Centre Léon Bérard
name: Isabelle Ray-Coquard, MD
role: PRINCIPAL_INVESTIGATOR
References: