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

Endometrial Cancer Clinical Trial

— ENDOPIK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01397877
• Other study ID #: ENDOPIK
• Status: Completed
• Phase: Phase 2
• Start date: December 2011
• Est. completion date: March 2016

Study information

• Verified date: September 2023
• Source: ARCAGY/ GINECO GROUP
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2016
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• BKM120
per os, 60mg/j, until progression or unacceptable toxicity

Locations

Country	Name	City	State
France	Clinique Bonnefon	Ales
France	Centre Paul Papin	Angers
France	Institut Ste Catherine	Avignon
France	Hôpital jean Minjoz	Besancon
France	Centre Hospitalier de Blois	Blois
France	Clinique Tivoli	Bordeaux
France	Institut Bergonié	Bordeaux
France	Polyclinique Bordeaux Nord	Bordeaux
France	centre Francois baclesse	Caen
France	Centre jean Perrin	Clermont Ferrand
France	Hôpitaux Civils de Colmar	Colmar
France	Centre Georges François leclerc	Dijon
France	Group Hospitalier Mutualiste de Grenoble	Grenoble
France	Hôpital Michallon - CHU Grenoble	Grenoble
France	CHD Les Oudairies	la Roche sur Yon
France	Hôpital André Mignot	Le Chesnay
France	Centre jean Bernard	Le Mans
France	Centre Oscar Lambret	Lille
France	CHU Dupuytren	Limoges
France	Centre Léon bérard	Lyon
France	Hôpital Prové Clairval	Marseille
France	institut Paoli Calmette	Marseille
France	CRLC Val d'Aurelle	Montpellier
France	Groupement de coopération sanitaire	Montpellier
France	Centre Alexis Vautrin	Nancy
France	Centre d'oncologie de Gentilly	Nancy
France	Centre Catherine de Sienne	Nantes
France	Centre Antoine Lacassagne	Nice
France	CHU Caremeau	Nimes
France	Clinique Valdegour	Nimes
France	Centre Hospitalier Régional	Orléans
France	Hopital Hotel Dieu	Paris
France	Hopital Tenon	Paris
France	Centre Eugene Marquis	Rennes
France	Centre Frederic Joliot	Rouen
France	Centre Henri Becquerel	Rouen
France	Clinique Armoricaine de Radiologie	Saint Brieuc
France	Hôpital rené Huguenin	St Cloud
France	ICO René Gauducheau	St Herblain
France	Centre Etienne DOLET	St Nazaire
France	Institut cancérologuie de la loire	St Priest en Jarez
France	Hôpital Civil	Strasbourg
France	Centre Claudius Régaud	Toulouse
France	CHU Bretonneau	Tours
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
ARCAGY/ GINECO GROUP

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Efficacy: PFS	To evaluate progression-free survival	6 months
Secondary	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
Secondary	Efficacy: overall survival	To evaluate overall survival.	Patients will be followed for an expected average of 1 year and 75 days
Secondary	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