Brief Title
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
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
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Clinical Efficacy
Secondary Outcome
Safety according to CTCAE v4.0 criteria and mood questionnaires : PHQ-9 and GAD-7
Condition
Endometrial Cancer
Intervention
BKM120
Study Arms / Comparison Groups
stratum 1
Description: Patients with low grade disease (grade 1 or 2) with positive or negative mutational status
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
24
Start Date
December 2011
Completion Date
March 2016
Primary Completion Date
October 2014
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Isabelle Ray-Coquard, MD, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT01397877
Organization ID
ENDOPIK
Responsible Party
Sponsor
Study Sponsor
ARCAGY/ GINECO GROUP
Study Sponsor
Isabelle Ray-Coquard, MD, Principal Investigator, GINECO - Centre Léon Bérard
Verification Date
March 2016