Clinical Trials Register

Summary
EudraCT Number:	2011-002576-16
Sponsor's Protocol Code Number:	GINECO-EN102b
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-07-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2011-002576-16

A.3

Full title of the trial

Phase 2 multicenter study to assess the safety and efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line therapy in patients who cannot undergo local surgery and/or radiotherapy.

Etude multicentrique de phase 2 évaluant la tolérance et l’efficacité du BKM120 en monothérapie dans le cancer de l’endomètre métastatique d’emblée ou en rechute après une première ligne, chez des patientes ne pouvant être traitées avec une chirurgie locale et/ou une radiothérapie.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

ENDOPIK

A.4.1

Sponsor's protocol code number

GINECO-EN102b

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ARCAGY
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ARCAGY
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ARCAGY
B.5.2	Functional name of contact point	Sponsor office
B.5.3	Address:
B.5.3.1	Street Address	Hôpital Hôtel-Dieu, 1, place du Parvis Notre-Dame
B.5.3.2	Town/ city	Paris cedex 4
B.5.3.3	Post code	75181
B.5.3.4	Country	France
B.5.4	Telephone number	33142348323
B.5.5	Fax number	33143262673
B.5.6	E-mail	vthouviot@arcagy.org

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	BKM120
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

initial or recurrent metastatic endometrial cancer after first line therapy in patients who cannot undergo local surgery and/or radiotherapy.

E.1.1.1

Medical condition in easily understood language

metastatic endometrial cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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).

E.2.2

Secondary objectives of the trial

• 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.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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.

E.5 End points

E.5.1

Primary end point(s)

Non-progression rate according to RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

at 3 (stratum 1) or 2 months (stratum 2)

E.5.2

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

E.5.2.1

Timepoint(s) of evaluation of this end point

during all the time of the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

12 months after the last follow up visit of the last subject.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

standard of care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-08-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-11

P. End of Trial
P.	End of Trial Status	Completed

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