Clinical Trials Register

Summary
EudraCT Number:	2013-003839-30
Sponsor's Protocol Code Number:	D081CC00006
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-04-15
Trial 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-003839-30

A.3

Full title of the trial

A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.

Studio randomizzato, in doppio cieco, a gruppi paralleli, controllato con placebo, multicentrico, di fase III per la valutazione dell'efficacia e della sicurezza di olaparib rispetto a placebo come trattamento adiuvante in pazienti con mutazioni germline del gene BRCA1/2, affetti da carcinoma mammario primitivo HER2 negativo ad alto rischio, che hanno completato il trattamento locale definitivo e la chemioterapia neoadiuvante o adiuvante

A.3.1

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

Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer.

Olaparib come trattamento adiuvante in pazienti con mutazioni germline del gene BRCA1/2, affetti da carcinoma mammario primitivo HER2 negativo ad alto rischio.

A.3.2

Name or abbreviated title of the trial where available

Olympia

A.4.1

Sponsor's protocol code number

D081CC00006

A.5.4

Other Identifiers

Name:

Protocol Study Code

Number:

BIG 6-13

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	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	Not Applicable
B.5.3.2	Town/ city	Not Applicable
B.5.3.3	Post code	Not Applicable
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@astrazeneca.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	olaparib
D.3.2	Product code	AZD2281
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.9.1	CAS number	763113-22-0
D.3.9.3	Other descriptive name	OLAPARIB
D.3.9.4	EV Substance Code	SUB32234
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	150
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	olaparib
D.3.2	Product code	AZD2281
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.9.1	CAS number	763113-22-0
D.3.9.3	Other descriptive name	OLAPARIB
D.3.9.4	EV Substance Code	SUB32234
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	100
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adjuvant breast cancer

carcinoma mammario avanzato

E.1.1.1

Medical condition in easily understood language

Breast cancer

carcinoma mammario

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	16.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS).

efficacia del trattamento adiuvante con olaparib sulla sopravvivenza libera da malattia invasiva (IDFS, Invasive Disease Free Survival)

E.2.2

Secondary objectives of the trial

- Efficacy of adjuvant treatment with olaparib on overall survival (OS).
- Efficacy of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS)
- Efficacy of adjuvant treatment with olaparib on the incidence of new invasive breast primary cancer and/or new epithelial ovarian cancer.
- Efficacy of olaparib on patient reported outcomes using the FACIT fatigue scale and EORTC QLQ-C30 QoL scale.
- Efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).

1.efficacia del trattamento adiuvante con olaparib sulla sopravvivenza globale (OS)
2.efficacia del trattamento adiuvante con olaparib sulla sopravvivenza libera da malattia a distanza (DDFS)
3.efficacia del trattamento adiuvante con olaparib sull'incidenza di nuovo carcinoma mammario invasivo primitivo e/o nuovo carcinoma ovarico epiteliale
4.efficacia di olaparib sugli esiti riferiti dai pazienti utilizzando la scala di valutazione dell'affaticamento FACIT e la scala di valutazione della qualità della vita QLQ-C30 dell'EORTC
5.efficacia di olaparib in pazienti nei quali è stata identificata una variante deleteria o sospetta deleteria in uno dei geni BRCA utilizzando varianti identificate con dosaggi attuali e futuri di determinazione della mutazione germline del gene BRCA (sequenziamento genico e analisi di riarrangiamento esteso)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histologically confirmed non-metastatic primary triple negative invasive adenocarcinoma of the breast.
-Invasive TNBC
-Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
- Completed adequate breast and axilla surgery. Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed.
-ECOG 0-1.

•Pazienti con diagnosi istologica di adenocarcinoma della mammella triplo negativo non metastatico.
•Tumore della mammella triplo negativo invasivo
•Mutazione documentata in BRCA1 or BRCA2 che si prevede sia, o si sospetta essere, deleteria (nota per essere o prevista essere dannosa/che porta a perdita di funzione).
•Intervento chirurgico completo della mammella comprensivo dei linfonodi ascellari
•Precedente trattamento di almeno 6 cicli chemioterapia neoadiuvanti o adiuvanti a base di antraci cline, taxani o la combinazione di entrambi. Pazienti che hanno ricevuto platino come trattamento potenzialmente curativo per precedenti tumori (es. tumore all’ovaio) o come trattamento adiuvante/neoadiuvante per il carcinoma della mammella.
•ECOG 0-1

E.4

Principal exclusion criteria

- Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the
excipients of study treatment.
- Patients with second primary cancer, EXCEPTIONS: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years prior to randomization. More than one course of chemotherapy for previous malignancies.
-Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc ≤470 msec.
- Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.-Whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing

•Precedente trattamento con inibitori PARP, incluso Olaparib e/o nota ipersensibilità a qualsiasi eccipiente del prodotto.
•Pazienti con un secondo tumore primario, ECCEZIONI: tumore della pelle che non sia melanoma, adeguatamente trattato, cancro della cervice trattato in-situ in modo curativo, Carcinoma Duttale in Situ (DCIS), carcinoma endometriale stadio 1 grado 1, o altri tumori solidi inclusi i linfomi (senza coinvolgimento del midollo osseo) trattati in modo curativo senza evidenza di malattia per ≥ 5 anni prima dell’ingresso nello studio. Più di un trattamento chemioterapico per tumori precedenti.
•ECG a riposo con QTc > 470 msec rilevato in 2 o più tempi entro un periodo di 24 ore o storia familiare di sindrome del QT lungo. Se ECG mostra QTc > 470 msec, il paziente sarà eleggibile solo se ECG ripetuti mostrano QTc ≤ 470 msec.
•Uso concomitante di potenti inibitori del CYP3A4 noti come ketoconazolo, itraconazolo, ritonavir indinavir, saquinavir, telitromicina, claritromicina e nelfinavir.
•Trasfusioni di sangue intero nei 120 giorni precedenti all’arruolamento nello studio, che potrebbero interferire con il test gBRCA .

E.5 End points

E.5.1

Primary end point(s)

Invasive Disease Free Survival (IDFS)

Sopravvivenza libera da malattia invasiva (IDFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Recurrent/new cancers assessments will be performed at day 1, weeks 12, 24, 38, 52. In follow-up period in year 2 every 3 months, in year 3, 4,5 every 6 months and year 6 to 10 every 12 months. MRI to be performed every 12 months after the 6 months scan.

Valutazioni di nuovi/ ricorrenti tumori verranno effettuate al giorno 1, settimane 12, 24, 38, 52.
Durante il periodo di follow up del secondo anno, verranno effettuate ogni 3 mesi, nel terzo, quarto e quinto anno ogni 6mesi, e dal sesto al decimo anno di follow up ogni 12 mesi.
La risonanza magnetica (MRI) verrà effettuata ogni 12 mesi, ad una distanza di 6 mesi dalla TAC.

E.5.2

Secondary end point(s)

1. Efficacy of adjuvant treatment with olaparib on overall survival (OS).
2. Efficacy of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS)
3. Efficacy of adjuvant treatment with olaparib on the incidence of new invasive breast primary cancer and/or new epithelial ovarian cancer.
4. Efficacy of olaparib on patient reported outcomes using the FACIT fatigue scale and EORTC QLQ-C30 QoL scale.
5. Efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).

1.efficacia del trattamento adiuvante con olaparib sulla sopravvivenza
globale (OS)
2.efficacia del trattamento adiuvante con olaparib sulla sopravvivenza
libera da malattia a distanza (DDFS)
3.efficacia del trattamento adiuvante con olaparib sull'incidenza di nuovo
carcinoma mammario invasivo primitivo e/o nuovo carcinoma ovarico
epiteliale
4.efficacia di olaparib sugli esiti riferiti dai pazienti utilizzando la scala di
valutazione dell'affaticamento FACIT e la scala di valutazione della
qualità della vita QLQ-C30 dell'EORTC
5.efficacia di olaparib in pazienti nei quali è stata identificata una variante deleteria o sospetta deleteria in uno dei geni BRCA utilizzando
varianti identificate con dosaggi attuali e futuri di determinazione della
mutazione germline del gene BRCA (sequenziamento genico e analisi di
riarrangiamento esteso)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Day 1, 15, 29 week 8,12,16,20,24,38,52, 30 days after last dose of study medication, in year 2 every 3 months, in year 3, 4,5 every 6 months and above year 6 every 12 months
2 & 3.Physical examination will be performed at day 1, weeks 12, 24, 38, 52. In follow-up period in year 2 every 3 months, in year 3, 4,5 every 6 months and year 6 to 10 every 12 months. MRI to be performed every 12 months after the 6 months scan
4.EORTC QLQ-C30 and FACIT-Fatigue scale will be collected prior randomization, at weeks 24 and 52 and also every 6 months during the 2nd year post randomisation (months 18 and 24 only).
5. Within 15 years from last subject last visit

1. gg 1, 15, 29 settimana 8,12,16,20,24,38,52, 30 giorni dopo l’ultima dose di farmaco, nel second anno ogni 3 mesi, negli anni 3, 4,5 ogni 6
Mesi e oltre il sesto anno ogni 12 mesi.
2 & 3.GLi esami fisicisaranno effettuati al giorno 1, settimana 12, 24, 38,
52. Durante il periodo di follow up del secondo anno, verranno effettuate ogni 3 mesi, nel terzo, quarto e quinto anno ogni 6mesi, e dal sesto al decimo anno di follow up ogni 12 mesi.La risonanza magnetica (MRI) verrà effettuata ogni 12 mesi, ad una distanza di 6 mesi dalla TAC.4.Il questionario EORTC QLQ-C30e la scala FACIT-Fatigue saranno raccolti prima della randomizzazione, e alla settimana 24 e 52 e anche ogni 6 mesi durante il secondo anno succesivo alla randomizzazione (solo ai mesi 18 e 24).
5. Entro 15 anni dal LSLV

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

224

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Canada

China

France

Italy

Japan

Austria

Netherlands

Portugal

Sweden

Argentina

Australia

Germany

Korea, Republic of

Spain

Israel

Poland

Switzerland

Taiwan

United Kingdom

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

Last subject last visit

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

660

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

660

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

873

F.4.2.2

In the whole clinical trial

1320

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

2014-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-05

P. End of Trial
P.	End of Trial Status	Ongoing

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