Clinical Trials Register

Summary
EudraCT Number:	2016-003163-20
Sponsor's Protocol Code Number:	CO-338-063
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:	2017-06-09
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

Spain - AEMPS

A.2

EudraCT number

2016-003163-20

A.3

Full title of the trial

TRITON3: A Multicenter, Randomized, Open-label Phase 3 Study of Rucaparib versus Physician’s Choice of Therapy for Patients with Metastatic Castration-resistant Prostate Cancer Associated with Homologous Recombination Deficiency

TRITON3: Estudio en fase III, multicéntrico, aleatorizado y abierto de rucaparib frente al tratamiento elegido por el médico para pacientes con cáncer de próstata metastásico resistente a la castración asociado a una deficiencia en la recombinación homóloga

A.3.1

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

A study to evaluate Rucaparib versus physician’s choice of therapy in patients with metastatic castration-resistant prostate cancer

Un estudio para evaluar Rucaparib en comparación con otro tratamiento a elección del médico en pacientes con cáncer de próstata metastásico resistente a la castración

A.3.2

Name or abbreviated title of the trial where available

TRITON3

A.4.1

Sponsor's protocol code number

CO-338-063

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02975934

A.5.4

Other Identifiers

Name:

IND

Number:

129,840

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	Clovis Oncology, Inc.
B.1.3.4	Country	United States
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	Clovis Oncology, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clovis Oncology UK Ltd
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	Sheraton House, Castle Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB3 0AX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+34658271136
B.5.6	E-mail	info@clovisoncology.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	Rucaparib 200mg
D.3.4	Pharmaceutical form	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	Rucaparib
D.3.9.1	CAS number	283173-50-2
D.3.9.2	Current sponsor code	CO-338
D.3.9.3	Other descriptive name	RUCAPARIB
D.3.9.4	EV Substance Code	SUB74859
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	200
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	Rucaparib 250 mg
D.3.4	Pharmaceutical form	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	Rucaparib
D.3.9.1	CAS number	283173-50-2
D.3.9.2	Current sponsor code	CO-338
D.3.9.3	Other descriptive name	RUCAPARIB
D.3.9.4	EV Substance Code	SUB74859
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	250
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: 3
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	Rucaparib 300 mg
D.3.4	Pharmaceutical form	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	Rucaparib
D.3.9.1	CAS number	283173-50-2
D.3.9.2	Current sponsor code	CO-338
D.3.9.3	Other descriptive name	RUCAPARIB
D.3.9.4	EV Substance Code	SUB74859
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	300
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: 4
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Docetaxel Hospira 10 mg/ml Concentrate for Solution for Infusion, 160mg/16ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Docetaxel Hospira 10 mg/ml Concentrate for Solution for Infusion
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	doxetaxel
D.3.9.4	EV Substance Code	SUB12492MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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: 5
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Xtandi 40 mg soft capsules
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Xtandi 40 mg soft capsules
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Capsule, soft
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	ENZALUTAMIDE
D.3.9.1	CAS number	915087-33-1
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
D.3.9.4	EV Substance Code	SUB77412
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	40
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: 6
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Zytiga 250 mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Zytiga 250 mg tablets
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	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	Abiraterone
D.3.9.1	CAS number	154229-18-2
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
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	250
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

Metastatic castration-resistant prostate cancer

cáncer de próstata metastásico resistente a la castración

E.1.1.1

Medical condition in easily understood language

advanced prostate cancer

cáncer de próstata avanzado

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate 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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10076506
E.1.2	Term	Castration-resistant prostate 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 assess the efficacy of rucaparib versus physician’s choice of treatment based on radiographic progression free survival (rPFS) in metastatic castration-resistant prostate cancer (mCRPC) patients with Homologous Recombination Deficiency (HRD) who progressed on prior AR-directed therapy and have not yet received chemotherapy in the castration-resistant setting.

Evaluar la eficacia de rucaparib frente al tratamiento elegido por el médico basado en la supervivencia sin progresión radiográfica (SSPr) en pacientes con CPRCm con DRH que progresaron con el tratamiento dirigido a los RA anterior y que no han recibido aún quimioterapia en el entorno resistente a la castración.

E.2.2

Secondary objectives of the trial

• To assess objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in patients with measurable (nodal or visceral) disease
• To assess duration of response (DOR) using modified RECIST Version 1.1 in patients with measurable (nodal or visceral) disease
• To assess time to PSA progression
• To assess PSA response > or = 50% (all patients)
• To assess PSA response > or = 90% (all patients)
• To evaluate Patient-reported Outcome (PRO) using the EuroQol 5 dimensions questionnaire (EQ-5D), Functional Assessment of Cancer Therapy–Prostate (FACT-P), analgesic drug score, and Brief Pain Inventory–Short Form (BPI-SF) instruments
• To assess clinical benefit rate (CBR)
• To assess overall survival (OS)
• To assess sparse pharmacokinetics (PK)
• To assess safety and tolerability

•Evaluar la tasa de respuesta objetiva (TRO) usando los criterios modificados de evaluación de la respuesta en tumores sólidos (RECIST), versión 1.1, en pacientes con enfermedad (ganglionar o visceral) medible
•Evaluar la duración de la respuesta (DR) usando los criterios RECIST modificados, versión 1.1, en pacientes con enfermedad (ganglionar o visceral) medible
•Evaluar el tiempo hasta la progresión del PSA
•Evaluar la respuesta del PSA > o = 50 % (todos los pacientes)
•Evaluar la respuesta del PSA > or = 90 % (todos los pacientes)
•Evaluar los resultados comunicados por el paciente (RCP) usando los instrumentos EQ-5D, Evaluación funcional del tratamiento del cáncer de próstata (FACT-P), puntuación de analgésicos e Inventario breve del dolor, versión abreviada (BPI-SF)
•Evaluar la tasa de beneficio clínico (TBC)
•Evaluar la supervivencia general (SG)
•Evaluar las muestras aisladas de farmacocinética (FC)
•Evaluar la seguridad y la tolerabilidad

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be > or = 18 years old at the time the informed consent is signed
2. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate
3. Be surgically or medically castrated, with serum testosterone levels of < or = 50 ng/dL (1.73 nM)
4. Be eligible for treatment with physician's choice of comparator treatment
5. Experienced of disease progression after treatment with 1 prior next generation AR targeted therapy (abiraterone acetate, enzalutamide, or investigational AR targeted agent) for castration resistant disease
6. Have a deleterious mutation in BRCA1/2 or ATM

1. Tener como mínimo 18 años de edad en el momento de firmar el consentimiento informado
2. Tener un adenocarcinoma confirmado histológica o citológicamente o un carcinoma poco diferenciado de la próstata
3. Paciente castrado quirúrgicamente o médicamente, con niveles de testosterona en suero < 50 ng/dl (< 1,73 nM)
4. Apto para el tratamiento comparador elegido por el médico
5. Indicios de progresión de la enfermedad tras el tratamiento con 1 tratamiento previo dirigido a los RA de última generación (acetato de abiraterona, enzalutamida o fármaco dirigido a los RA en investigación) para la enfermedad resistente a la castración
6. Signos moleculares de CPRCm asociados con una mutación genética en BRCA1/2 o ATM nociva.

E.4

Principal exclusion criteria

1. Active second malignancy, with the exception of curatively treated non melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
2. Prior treatment with any PARP inhibitor
3. Prior treatment with chemotherapy for mCRPC
4. Symptomatic and/or untreated central nervous system metastases
5. Pre existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of study drug

1. Neoplasia maligna secundaria, con la excepción de cáncer de piel no melanoma tratado con éxito, carcinoma in situ o cáncer de vejiga superficial
2. Tratamiento previo con cualquier iPARP
3. Tratamiento previo con quimioterapia administrado para la enfermedad resistente a la castración.
4. Metástasis sintomáticas y/o no tratadas del sistema nervioso central (SNC).
5. Endoprótesis duodenal preexistente y/o cualquier trastorno o defecto gastrointestinal que, en opinión del investigador, interfiera con la absorción del fármaco del estudio

E.5 End points

E.5.1

Primary end point(s)

Efficacy of rucaparib versus physician’s choice of treatment based on
radiographic progression free survival (rPFS) in mCRPC patients with HRD who progressed on prior AR-directed therapy and have not yet received chemotherapy in the castration-resistant setting.

Eficacia de rucaparib versus el tratamiento de elección del médico en base a supervivencia sin progresión radiográfica (SSPr) en pacientes con CPRCm con DRH que progresaron con el tratamiento dirigido a los RA anterior y que no han recibido aún quimioterapia en el entorno resistente a la castración

E.5.1.1

Timepoint(s) of evaluation of this end point

Tumor assessments will be performed during screening (baseline), at the end of every 8 calendar weeks (+/-7 days) relative to Study Day 1 (Week 1) up to 24 weeks, then every 12 calendar weeks (+/-7 days), until confirmed radiographic disease progression by modified RECIST Version 1.1 and/or PCWG3 (for bone lesions only) criteria, as assessed by IRR, loss to follow-up, withdrawal, or study closure. Tumor assessments will continue to be performed until radiographic disease progression is confirmed by IRR.

E.5.2

Secondary end point(s)

• Objective response rate (ORR) assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in patients with measurable (nodal or visceral) disease
• Duration of response (DOR) using modified RECIST Version 1.1 in patients with
measurable (nodal or visceral) disease
• time to PSA progression
• PSA response > or = 50% (all patients)
• PSA response > or = 90% (all patients)
• Patient-reported Outcome (PRO) using the EuroQol 5 dimensions questionnaire (EQ-5D), Functional Assessment of Cancer Therapy–Prostate (FACT-P), analgesic drug score, and Brief Pain Inventory–Short Form (BPI-SF) instruments
• clinical benefit rate (CBR)
• overall survival (OS)
• sparse pharmacokinetics (PK)

Safety Analyses
Adverse events (AEs), clinical laboratory results, vital signs, ECOG performance status, body weight, and concomitant medications/ procedures will be tabulated and summarized.

•tasa de respuesta objetiva (TRO) usando los criterios modificados de evaluación de la respuesta en tumores sólidos (RECIST), versión 1.1, en pacientes con enfermedad (ganglionar o visceral) medible
•duración de la respuesta (DR) usando los criterios RECIST modificados, versión 1.1, en pacientes con enfermedad (ganglionar o visceral) medible
•tiempo hasta la progresión del PSA
•respuesta del PSA > o = 50 % (todos los pacientes)
•respuesta del PSA > or = 90 % (todos los pacientes)
•resultados comunicados por el paciente (RCP) usando los instrumentos EQ-5D, Evaluación funcional del tratamiento del cáncer de próstata (FACT-P), puntuación de analgésicos e Inventario breve del dolor, versión abreviada (BPI-SF)
•tasa de beneficio clínico (TBC)
•supervivencia general (SG)
•muestras aisladas de farmacocinética (FC)

Análisis de seguridad:
Se tabularán y resumirán los acontecimientos adversos (AA), resultados de analíticas, constantes vitales, ECOG, peso corporal, medicación concomitante y procedimientos

E.5.2.1

Timepoint(s) of evaluation of this end point

Tumor assessments will be performed during screening (baseline), at the end of every 8 calendar weeks (±7 days) relative to Study Day 1 (Week 1) up to 24 weeks, then every 12 calendar weeks (±7 days), until confirmed radiographic disease progression by modified RECIST Version 1.1 and/or PCWG3 (for bone lesions only) criteria, as assessed by IRR, loss to follow-up, withdrawal, or study closure. Tumor assessments will continue to be performed until radiographic disease progression is confirmed by IRR.

PSA will be measured locally at Screening, Day 1, every 28 days thereafter, and at the Treatment Discontinuation Visit.

OS will be monitored until patient death.

PK will be collected on Study Day 29, Day 57, Day 85, and Day 113.

Safety will be monitored at all visits

Se realizarán evaluacines tumorales durante la selección (basal), al final de cada 8 semanas (+/-7 días) desde el dia 1 (semana 1) y hasta las 24 semanas, posteriormente cada 12 semanas (+/- 7 días), hasta confirmación de progresión según RECIST 1.1 y/o PCWG3 (para lesiones óseas únicamente), tal y como lo evalue un revisor independiente, pérdida de seguimiento, retirada o cierre del estudio. Las evaluaciones tumorales se seguirán realizando hasta progresión radiológica confirmada por revisor independiente
El PSA se medirá localmente en visita de selección, día 1, cada 28 días y posteriormente en la visita de interrupción del tratamiento
La SG se monitorizará hasta la muerte del paciente
Se recogerán muestras de FC los días 29, 57, 85 y 113
La seguridad se monitorizará en cada visita

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

Belgium

Canada

Denmark

France

Germany

Ireland

Israel

Italy

Spain

Switzerland

United Kingdom

United States

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

LVLS

Última visita del último paciente

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:

160

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

240

F.2 Gender

F.2.1

Female

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

160

F.4.2.2

In the whole clinical trial

400

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)

All patients will continue on standard of care.

Also upon formal closure of the study, individual patients who are continuing to benefit from treatment with rucaparib at the time of study closure, and who do not meet any of the criteria for withdrawal, will have the option of entering an extension protocol in which they can continue to receive rucaparib.

Todos los pacientes continuarán con tratamiento estándar
Además, antes del cierre formal del estudio, los pacientes que continuen beneficiándose del tratamiento con rucaparib en ese momento y que no hayan cumplido ningún criterio para la retirada tendrán la opción de entrar en un estudio de extensión en el que seguir el tratamiento con rucaparib

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

2017-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-26

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