Clinical Trials Register

Summary
EudraCT Number:	2013-001211-75
Sponsor's Protocol Code Number:	D0816C00002
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-07-30
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2013-001211-75

A.3

Full title of the trial

A Phase III Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy

Ensayo fase III, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de mantenimiento con Olaparib en monoterapia en pacientes con cáncer de ovario con mutación de BRCA y recaída platino sensible, que están en respuesta completa o parcial después de una quimioterapia basada en platino

A.3.1

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

Olaparib treatment in BRCA Mutated Ovarian Cancer patients after Complete or Partial Response to Platinum Chemotherapy

Tratamiento con Olaparib en pacientes con cáncer de ovario con mutación de BRCA tras respuesta parcial o completa a la quimioterapia basada en platino.

A.3.2

Name or abbreviated title of the trial where available

OSTRIA 2

A.4.1

Sponsor's protocol code number

D0816C00002

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/501
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.3.8	INN - Proposed INN	Olaparib
D.3.9.1	CAS number	763113-22-0
D.3.9.2	Current sponsor code	AZD2281
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.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/501
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.3.8	INN - Proposed INN	Olaparib
D.3.9.1	CAS number	763113-22-0
D.3.9.2	Current sponsor code	AZD2281
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.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

BRCA Mutated Platinum Sensitive Relapse (PSR) high grade Serous Ovarian Cancer

cáncer de ovario seroso de alto grado con mutación de BRCA recidivante y sensible al platino (RSP).

E.1.1.1

Medical condition in easily understood language

Ovarian cancer

Cáncer de ovario

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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10014733
E.1.2	Term	Endometrial 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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10061269
E.1.2	Term	Malignant peritoneal neoplasm
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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10016180
E.1.2	Term	Fallopian tube 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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian 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

Determine the efficacy by progression free survival of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Determinar la eficacia de Olaparib en monoterapia de mantenimiento en comparación con placebo en pacientes con cáncer de ovario recidivante con mutación de BRCA que están en respuesta parcial o completa después de quimioterapia basada en platino, mediante supervivencia libre de progresión (SLP).

E.2.2

Secondary objectives of the trial

1. Efficacy in patients following Platinum Based Chemotherapy by assessment of overall survival
2. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen (CA-125)
3. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Efficacy in patients following Platinum Based Chemotherapy by assessment of time from randomisation to second progression
4. Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O
5. Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS.
6. To determine the exposure to Olaparib
7. Safety and tolerability of olaparib by assessment of the number of AEs and review of laboratory parameters

1. Eficacia en pacientes tras quimioterapia basada en platino, mediante la valoración de la supervivencia global. 2. Eficacia en pacientes tras quimioterapia basada en platino, mediante valoración del tiempo hasta la primera progresión por RECIST o antígeno de cáncer-125 (CA-125). 3. Eficacia en pacientes tras quimioterapia basada en platino mediante la valoración del tiempo hasta la primera progresión tras la quimioterapia basada en platino o tiempo desde la randomización hasta la segunda progresión. 4. Tiempo en el deterioro de la calidad de vida relacionada con la salud (CdVRS), evaluada mediante IRE y FACT-O. 5. Eficacia en pacientes con variante deletérea o de la que se sospecha que es deletérea en cualquiera de los genes de BRCA evaluada mediate valoración de SLP. 6. Determinar la exposición a olaparib. 7. Seguridad y tolerabilidad a olaparib evaluada mediante el número de AAs y revisión de los parámetros de laboratorio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Patients must be ? 18 years of age.
-Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.
-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).
-Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation For the penultimate chemotherapy course prior to enrolment on the study:
-Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy For the last chemotherapy course immediately prior to randomisation on the study:
-Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, following completion of this chemotherapy course
- Patient must have received a platinum based chemotherapy regimen carboplatin or cisplatin) and have received at least 4 cycles of treatment

-pacientes deben tener ? 18 años.
-pacientes mujeres con cáncer de ovario resoso o de alto grado (incluido cáncer peritoneal primario y/cáncer de la trompa de falopio) o endometriode de alto grado
Mutación documentada de BRCA1o BRCA2 que se predice que es deletérea o se sospecha que es deletérea (se sabe o se predice que es perjudicial/conduce a pérdia de la función)
-Pacientes que han recibido al menos 2 línea previas de terapia con platino antes de la aleatorizacion
Para el penúltimo tratamiento de quimioterapia antes de la inclusión en el ensayo:
-Pacientes definida como sensible al platino despues del tratamiento; se define como la progresión de la enfermedad más de 6 meses despues de la terminación de su última dosis de quimioterapia con platino
-pacientes que en opinión del investigador deben estar en respuesta (respuesta radiológica parcial o completa) o pueden no tener indicios de elevacion de CA-125 como se define a continuación, despues de la terminación de este tratamiento de quimioterapia
- pacientes que han recibido un régimen de quimioterapia basado en platino (carboplatino y cisplatino) y haber recibido al menos 4 ciclos de tratamiento

E.4

Principal exclusion criteria

- Involvement in the planning and/or conduct of the study (applies to
both AstraZeneca staff and/or staff at the study site).
-BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., ?Variants of uncertain clinical significance? or ?Variant of unknown significance? or ?Variant, favor polymorphism? or ?benign polymorphism? etc.)
-Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.

-Participación en la planificación y/o realización del ensayo (se aplica tanto al personal de AstraZeneca como al personal del centro
-Mutaciones de BRCA 1 y/o BRCA2 que se consideran no perjudiciales(p. ej, "variantes de significación clínica o incierta" o " Variante de significación desconocida" o "Variante, a favor de polimorfismo" o "polimorfismo benigno", etc)
-Pacientes que se han sometido a drenaje de sus ascitis durante los 2 ciclos finales de su último régimen de quimioterapia antes del reclutamineto en el ensayo

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS) by central review of RECIST data.

Supervivencia libre de progresión (SLP) mediante revisión central de los datos de RECIST

E.5.1.1

Timepoint(s) of evaluation of this end point

Radiologic scans performed at base line then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression.
Study data collection expected to last until 2018.

Se realizarán evaluaciones radiológicas en el momento basal cada 12 semanas hasta las 72 semanas y luego cada 24 semanas hasta la progresión radiológica objetiva de la enfermedad
Se prevee que la recogida de datos sea hasta el 2018

E.5.2

Secondary end point(s)

1. Efficacy in patients following Platinum Based Chemotherapy by assessment of overall survival
2. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen (CA-125) or death
3. Efficacy in patients following Platinum Based Chemotherapy by assessment of time from randomisation to second progression
4. Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O
5. Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS.
6. To determine the exposure to Olaparib by Pharmacokinetic analysis
7. Safety and tolerability of olaparib by assessment of the number of AEs and review of laboratory parameters

E.5.2.1

Timepoint(s) of evaluation of this end point

Data collection expected until 2018, for all except Pk endpoint 6
1. Survival assessed every 4 wks until treatment discontinues, then every 12 wks.
2. CA-125, baseline then every 4 wks. Radiological scans, base line, every ~12 wks until obj radiological disease prog
3. Radiologic scans, baseline, every 12 wks for 72 wks, every 24 wks until 1st prog. As per local practice until 2nd prog
4. Paper Q's at baseline, Day 29 then in line with RECIST, until disease prog
5. Radiological scans baseline, every ~12 wks for 1st 72 wks, every ~24 wks, until disease prog
6. Pk in a subset of patients. Sample times: Day 1+15 pre-dose & 1 hr; Day 29 pre-dose, 0.5-1, 1-3, 3-6 and 6-12 hrs.
7. AEs from inf cons until post treatment 30-day follow-up period. Labs until treatment discontinued.

Se prevé la recogida de datos hasta 2018, para todas las variables, excepto para la variable de valoración 6 de FC. 1. Supervivencia valorada cada 4 semanas hasta la discontinuación del tratamiento, y después cada 12 semanas. 2. C-125 en el momento basal y después cada 4 semanas. Evaluaciones radiológicas en el momento basal, después cada 12 semanas hasta progresión objetiva radiológica de la enfermedad. 3. Evaluaciones radiológicas en el momento basal, cada 12 semanas durante las primeras 72 semanas y después cada 24 semanas hasta progresión de la enfermedad. Según práctica local hasta la segunda progresión. 4. Cuestionarios de papes en el momento basal, día 29 y posteriormente en línea con las evaluaciones RECIST, has progresión de la enfermedad.

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

Yes

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

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

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

Australia

Brazil

Canada

China

France

Germany

Italy

Japan

Netherlands

Poland

Russian Federation

Spain

Sweden

United Kingdom

United States

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

LVLS (last visit last subject) undergoing the study

Última visita del último paciente en el ensayo

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:

132

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

132

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

112

F.4.2.2

In the whole clinical trial

264

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)

Patients who are receiving treatment can either choose to discontinue from the study, or where the investigator believes the patients are gaining clinical benefit, patients may continue to recieve study treatment.

Las pacientes que estén recibiendo el tratamiento activo pueden decidir abandonar el ensayo o, cuando el investigador crea que las pacientes están obteniendo beneficio

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	ARCAGY-GINECO, acting as lead group for ENGOT
G.4.3.4	Network Country	France

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-08-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-08-01

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

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