Clinical Trials Register

Summary
EudraCT Number:	2014-000599-24
Sponsor's Protocol Code Number:	iOM-02282
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-09-02
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2014-000599-24

A.3

Full title of the trial

Molecularly stratified parallel group phase II trial of the phosphoinositide 3-kinase (PI3K) inhibitor BKM120 in combination with tamoxifen in patients with hormone receptor-positive, HER2-negative inoperable (locally advanced or metastatic) breast cancer with prior exposure to antihormonal therapy

A.3.1

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

Clinical trial of BKM120 in combination with tamoxifen in patients with breast cancer (hormone receptor-positive, HER2-negative, inoperable, locally advanced or metastatic)

A.3.2

Name or abbreviated title of the trial where available

PIKTAM

A.4.1

Sponsor's protocol code number

iOM-02282

A.5.4

Other Identifiers

Name:	Study Code Novartis - IMP supply	Number:	CBKM120ZDE02T
Name:	Code of AIO	Number:	AIO-MAM-0114/ass

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	Universitätsklinikum Essen, Westdeutsches Tumorzentrum
B.1.3.4	Country	Germany
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	Novartis Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	iOMEDICO AG
B.5.2	Functional name of contact point	Contract Research Organization
B.5.3	Address:
B.5.3.1	Street Address	Hanferstrasse 28
B.5.3.2	Town/ city	Freiburg
B.5.3.3	Post code	79108
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49761152420
B.5.5	Fax number	+497611524210
B.5.6	E-mail	info@iomedico.com

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.3.1	Product name	Buparlisib
D.3.2	Product code	BKM120
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Buparlisib
D.3.9.1	CAS number	944396-07-0
D.3.9.2	Current sponsor code	BKM120
D.3.9.3	Other descriptive name	BUPARLISIB
D.3.9.4	EV Substance Code	SUB128477
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.IMP: 2
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.3.1	Product name	Buparlisib
D.3.2	Product code	BKM120
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Buparlisib
D.3.9.1	CAS number	944396-07-0
D.3.9.2	Current sponsor code	BKM120
D.3.9.3	Other descriptive name	BUPARLISIB
D.3.9.4	EV Substance Code	SUB128477
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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

The study population includes patients with histologically, progressive, inoperable (locally advanced or metastatic) hormone receptor (HR)–positive, HER2-negative breast cancer

E.1.1.1

Medical condition in easily understood language

The study population includes patients with progressive, inoperable (locally advanced or metastatic) hormone receptor (HR)–positive, HER2-negative breast cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10057654
E.1.2	Term	Breast cancer female
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10055113
E.1.2	Term	Breast cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10070577
E.1.2	Term	Oestrogen receptor positive breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 evaluate efficacy of BKM120 in combination with tamoxifen in patients with ER/PR-positive, HER2-negative breast cancer stratified to PIK3CA mutation and preserved PTEN expression, loss of PTEN expression +/- PIK3CA mutation or PIK3CA wild type and preserved PTEN expression

E.2.2

Secondary objectives of the trial

-To assess 6 month progression-free survival (PFS) rate.
-To assess progression-free survival (PFS)
-To explore overall survival (OS)
-To assess overall response rate (ORR)
-To assess disease control rate (DCR)
-To assess safety and tolerability throughout the study according to CTCAE v4.03
-To assess incidence and severity of depressive episodes during the course of treatment

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Prospective validation of biomarkers indicating phosphoinositide-3-kinase pathway activation for breast cancer treatment.
This substudy aims to improve “personalized” treatment options for patients with metastatic, estrogen receptor (ER)-positive breast cancer, the leading cause of breast cancer-related mor-tality in Germany. This shall be achieved by validating robust, highly sensitive and noninvasive technologies for detection of genomic biomarkers, by refinement of the diagnostic panel for prediction of response to pharmacologic inhibitors of the phosphoinositide-3-kinase (PI3K) pathway based on comprehensive genomic analyses, and prospectively by nominating novel therapeutic targets. Specific aims of the substudy are:
-To validate noninvasive detection assays of genomic biomarkers associated with PI3K pathway activation for prediction and monitoring of response to pharmacologic PI3K pathway modulation in ER-positive metastatic breast cancer.
-To develop and validate multiplexed, targeted biomarker profiling using next generation sequencing technology in diagnostic tumor samples from breast cancer patients pro-spectively enrolled in the screening and treatment phases of the PIKTAM study
-To conduct comprehensive genome analyses in diagnostic tumor samples (i) to identify novel and more refined genomic signatures associated with clinical outcome in response to pharmacologic PI3K pathway modulation, and (ii) to prospectively nominate novel therapeutic targets for improvement of PI3K-directed therapies in ER-positive metastatic breast cancer.

E.3

Principal inclusion criteria

-Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
-Patient has radiologic or objective evidence of inoperable locally advanced, or metastatic breast cancer
-Patient has a known hormone receptor status HR–positive (ER and/or PR positive) and HER2-negative status
-Patient has a representative archival formalin-fixed tumor biopsy (metastasis or primary tumor)
-Patient has prior exposure to antihormonal therapy
-Patient has received ≤ 2 prior antihormonal treatments in the metastatic setting
-Prior treatment with tamoxifen in the (neo-)adjuvant setting is allowed but has to be discontinued for at least 1 year.
-Patient may have received up to one prior chemotherapy in the metastatic setting
-Measurable or non-measurable lesions according to RECIST v1.1 criteria
-Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2

E.4

Principal exclusion criteria

-Patient has received previous treatment with a PI3K- or AKT-inhibitor or mTOR-inhibitors
-Prior treatment with Tamoxifen in the metastatic setting. Treatment with tamoxifen in the (neo-)adjuvant setting is allowed, but has to be discontinued for at least 1 year
-Patient has symptomatic CNS metastases
-Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM-IV).
-Patient has a known history of HIV infection (testing not mandatory) infection

E.5 End points

E.5.1

Primary end point(s)

Progression free survival (PFS)-rate in the full population, after 6 months of combination therapy, defined by local investigator assessment

E.5.1.1

Timepoint(s) of evaluation of this end point

after 6 months

E.5.2

Secondary end point(s)

-Progression free survival (PFS)- rate in the subpopulations after 6 months of combination therapy
-PFS in subpopulations and full population. PFS is defined as time from date of start of treatment to the date of the event, defined as the first documented disease progression or death due to any cause per local investigator assessment
-OS in subpopulations and full population. OS is defined as time from date of start of treatment to the date of death from any cause.
- ORR in subpopulations and full population. ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR)
- DCR in subpopulations and full population. DCR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 12 weeks
-Type, frequency and severity of adverse events per CTCAE v4.03
-Change in depressive episodes assessed by PHQ-9 questionnaire and GAD-7

E.5.2.1

Timepoint(s) of evaluation of this end point

after 6 months or end of 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

Yes

E.6.4

Safety

Yes

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

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

Yes

E.8.1.7.1

Other trial design description

molecularly stratified

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.8.3

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

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

The end of entire study is defined as the time point of last patient last visit, i.e. when the treatment period, safety follow-up, efficacy follow-up and survival follow up have ended for all patients.

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:

165

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

165

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

330

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)

If patients discontinue study treatment (e.g. due to progression, toxicity or regular end of treatment) the investigator will offer appropriate treatment options according to current knowledge and treatment standards.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-10-18

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials