Clinical Trials Register

Summary
EudraCT Number:	2011-003832-30
Sponsor's Protocol Code Number:	11-PIR-11
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-04-17
Trial results	View results

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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2011-003832-30

A.3

Full title of the trial

The BEACON Study (BrEAst Cancer Outcomes with NKTR-102): A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 versus Treatment of Physician?s Choice (TPC) in Patients with Locally Recurrent or Metastatic Breast Cancer Previously Treated with an Anthracycline, a Taxane, and Capecitabine

El estudio BEACON (BrEAst Cancer Outcomes with NKTR 102; Resultados del cáncer de mama con NKTR 102): Estudio de fase 3, abierto, aleatorizada y multicéntrico de NKTR 102 frente al tratamiento elegido por el médico (TEM) en pacientes con cáncer de mama localmente recurrente o metastásico tratadas previamente con una antraciclina, un taxano y capecitabina

A.3.1

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

Study to compare NKTR-102 (also called the "study drug") with standard treatments for breast cancer (also called "treatment of physician's choice").

Estudio para comparar NKTR-102 (también llamado "medicación de estuduio") frente a tratamientos estándar para cáncer de mana (también llamado "tratamiento elegido por el médico").

A.3.2

Name or abbreviated title of the trial where available

BEACON

A.4.1

Sponsor's protocol code number

11-PIR-11

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01492101

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	Nektar Therapeutics
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	Nektar Therapeutics
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	Quintiles Contact Center
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	n/a
B.5.3.2	Town/ city	n/a
B.5.3.3	Post code	n/a
B.5.3.4	Country	United States
B.5.4	Telephone number	n/an/a
B.5.5	Fax number	n/an/a

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	NKTR-102
D.3.4	Pharmaceutical form	Powder 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	Not Available
D.3.9.1	CAS number	1193151-06-2
D.3.9.2	Current sponsor code	NKTR-102
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	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	Abraxane
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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	Paclitaxel albumin
D.3.4	Pharmaceutical form	Suspension 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.3.9.1	CAS number	33069-62-4
D.3.9.3	Other descriptive name	Paclitaxel albumin
D.3.9.4	EV Substance Code	SUB09583MIG
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	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	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	Halaven
D.2.1.1.2	Name of the Marketing Authorisation holder	Eisai Europe Ltd
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	Eribulin (as mesylate)
D.3.4	Pharmaceutical form	Solution for injection
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.3.9.1	CAS number	441045-17-6
D.3.9.3	Other descriptive name	ERIBULIN MESYLATE
D.3.9.4	EV Substance Code	SUB31126
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	440
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	Gemcitabine
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Gemcitabine
D.3.4	Pharmaceutical form	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	GEMCITABINE HYDROCHLORIDE
D.3.9.1	CAS number	122111-03-9
D.3.9.4	EV Substance Code	SUB02324MIG
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	38
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	Navelbine
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Vinorelbine
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.3.9.1	CAS number	125317-39-7
D.3.9.3	Other descriptive name	VINORELBINE TARTRATE
D.3.9.4	EV Substance Code	SUB20777
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: 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	Docetaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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
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.3.9.1	CAS number	114977-28-5
D.3.9.3	Other descriptive name	Anhydrous Docetaxel
D.3.9.4	EV Substance Code	SUB22289
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: 7
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	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Paclitaxel
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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.4	EV Substance Code	SUB09583MIG
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	6
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

Locally Recurrent Breast Cancer, Metastatic Breast Cancer

Cáncer de Mama localmente recurrente, Cáncer de Mama metastásico

E.1.1.1

Medical condition in easily understood language

Metastasic Breast Cancer (MBC)

Cáncer de Mama Metastásico (CMM)

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10006198
E.1.2	Term	Breast cancer recurrent
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	14.1
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	14.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the Overall Survival (OS) of patients who receive NKTR-102 given once every 21 days to patients who receive TPC selected from the following list of seven single-agent intravenous therapies: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel,
docetaxel or nab-paclitaxel.

Comparar la supervivencia global (SG) de las pacientes que reciban NKTR 102 una vez cada 21 días (c21d) con la de las que reciban un tratamiento elegido por el médico (TEM) seleccionado de la siguiente lista de siete tratamientos por vía intravenosa en monoterapia: eribulina, ixabepilona, vinorrelbina, gemcitabina, paclitaxel, docetaxel o nab paclitaxel.

E.2.2

Secondary objectives of the trial

? To compare the Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (hereafter referred to as RECIST)
? To compare progression-free survival (PFS)
? To compare the Clinical Benefit Rate (CBR) (the proportion of patients having complete response (CR), partial response (PR), or
stable disease (SD) for at least 6 months)
? To compare Duration of Response (DoR)
? To determine the safety profiles of NKTR-102 and Treatment of Physician?s Choice (TPC) (including Grade 3 and higher toxicities, incidence of dose reductions and dose intensity)
? To compare health-related quality of life (QoL) using the QLQ-C30 questionnaire with the BR23 subscale
? To obtain pharmacokinetic (PK) data (in selected patients randomized to NKTR-102 only)
? To evaluate the pharmacoeconomic implications of NKTR-102 therapy using selected measures of health care utilization

? Comparar la tasa de respuesta objetiva (TRO) según los Criterios de evaluación de la respuesta en tumores sólidos (RECIST), versión 1.1 (en adelante, criterios RECIST).
? Comparar la supervivencia sin progresión (SSP).
? Comparar la tasa de efectos clínicos beneficiosos (TECB, proporción de pacientes con respuesta completa (RC), respuesta parcial (RP) o enfermedad estable (EE) durante al menos 6 meses).
? Comparar la duración de la respuesta (DR).
? Determinar los perfiles de seguridad de NKTR 102 y el TEM (toxicidad de grado 3 o superior, incidencia de reducciones de la dosis e intensidad de la dosis).
? Comparar la calidad de vida (CdV) relacionada con la salud con el cuestionario QLQ C30 y la subescala BR23.
? Obtener datos farmacocinéticos (FC) (solo en determinadas pacientes aleatorizadas a NKTR 102).
? Evaluar las consecuencias farmacoeconómicas del tratamiento con NKTR 102 con determinadas medidas de utilización de recursos sanitarios.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

?Patient is an adult female with histologically or cytologically confirmed carcinoma of the breast for whom single-agent cytotoxic chemotherapy is indicated
?Patient can have either measurable or non-measurable disease by RECIST.
?Patient has received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, a taxane and capecitabine
?Patient has minimum of 2 and a maximum of 5 prior cytotoxic chemotherapy regimens with the last dose administered within 6 months. A minimum of two chemotherapy regimens had to be for locally recurrent and/or metastatic disease. All therapy received prior to a diagnosis of metastatic disease (eg, neoadjuvant, adjuvant or repeated adjuvant therapy following a second resection) is counted as one regimen.
?Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
?Adequate hematopoietic, liver and kidney functions.

?Mujer con cáncer de mama (primario o lesiones metastásicas) confirmado mediante histología o citología en la que esté indicado el uso de quimioterapia citotóxica en monoterapia.
?Las pacientes podrán presentar enfermedad mensurable o enfermedad no mensurable según los criterios RECIST.
?Tratamiento previo (administrado en el contexto neoadyuvante, adyuvante o metastásico) con una antraciclina , un taxano y Capecitabina.
?Un mínimo de dos y un máximo de cinco regímenes previos de quimioterapia citotóxica con la última dosis de quimioterapia administrada en los 6 meses previos.

E.4

Principal exclusion criteria

?Patient with chemotherapy within 21 days, radiotherapy within 14 days, biological therapy with 14 days, hormonal therapy within 7 days and investigational therapy within 21 days prior to randomization.
?Patient with any major surgery within 28 days prior to randomization.
?Patient with concurrent use of biologic agents for the treatment of cancer including antibodies or any investigational agent(s).
?Patient with prior treatment for cancer with a camptothecin derivative.
?Patient with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care to control diarrhea in the 28 days prior to randomization.
?Patient received pharmacotherapy for hepatitis B or C, tuberculosis or HIV.
?Patient with known cirrhosis diagnosed with Child-PUGH Class A or higher liver disease.
?Patient with prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization.
?Patient requiring daily use of oxygen supplementation in the 28 days prior to randomization.
?Patients with significant cardiovascular impairment.

? Pacientes que hayan recibido quimioterapia en los 21 días, radioterapia en los 14 días, tratamiento biológico en los 14 días, tratamiento hormonal en los 7 días y tratamiento experimental en los 21 días anteriores a la aleatorización.
? Pacientes que se hayan sometido a una operación de cirugía mayor en los 28 días anteriores a la aleatorización.
? Pacientes con uso concomitante de productos biológicos para el tratamiento del cáncer, incluidos anticuerpos y cualquier producto en investigación.
? Pacientes que hayan recibido tratamiento previo contra el cáncer con un derivado de camptotecina.
? Pacientes con trastornos digestivos crónicos agudos que originen diarrea de cualquier grado de intensidad; pacientes que empleen tratamiento sintomático antidiarreico de forma crónica para controlar la diarrea en los 28 días anteriores a la aleatorización.
? Pacientes que estén recibiendo farmacoterapia contra la hepatitis B o C, la tuberculosis o el VIH.
? Pacientes con cirrosis conocida diagnosticadas de una hepatopatía en clase A o superior de Child Pugh.
? Pacientes con neoplasia maligna previa (distinta del cáncer de mama), excepto cáncer de piel distinto del melanoma y carcinoma in situ (de cuello uterino o vejiga), a menos que haya sido diagnosticada y tratada de forma definitiva más de 5 años antes de la aleatorización.
? Pacientes con necesidad de uso diario de oxigenoterapia en los 28 días anteriores a la aleatorización.
? Pacientes con nsuficiencia cardiovascular importante.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is OS

El criterio de valoración principal de la eficacia de este estudio será la SG.

E.5.1.1

Timepoint(s) of evaluation of this end point

Overall survival is defined as the time from the date of randomization to death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or alive at the time of analysis will be censored at the time they were last known alive.

La SG se define como el tiempo transcurrido entre la fecha de aleatorización y la muerte por cualquier causa. Se someterá a seguimiento a las pacientes hasta la fecha de la muerte o hasta el cierre definitivo de la base de datos. En las pacientes con las que se haya perdido el contacto durante el seguimiento o que estén vivas en el momento del análisis se censurarán los datos en la última fecha en que se tenga conocimiento de que estaban vivas.

E.5.2

Secondary end point(s)

? ORR
? PFS
? CBR
? DoR
? Incidence and severity of treatment-emergent adverse events (TEAEs), laboratory abnormalities, targeted symptoms (including diarrhea and neuropathy); incidence of dose reductions; dose intensity
? QLQ-C30 individual scale, overall score and BR23 score value and change over the time of study participation
? Derived PK parameters, including Cmax, AUC, time to Cmax (Tmax), V, elimination t½ and CL, with an exploratory analysis regarding possible correlation to various baseline characteristics (eg, age and UGT1A1 status)
? Selected measures of health care utilization
? Quantification of CTCs and assessment of various biomarkers (eg, topoisomerase 1 and 2 expression, DNA damage and apoptosis at baseline); change from baseline.

? TRO.
? SSP.
? TECB.
? DR.
? Incidencia e intensidad de los acontecimientos adversos aparecidos durante el tratamiento (AAAT), anomalías analíticas, síntomas de interés (como diarrea y neuropatía), incidencia de reducciones de la dosis, intensidad de la dosis.
? Escala individual QLQ C30, puntuación global y valor de la puntuación BR23 y variación con el tiempo durante la participación en el estudio.
? Parámetros FC derivados, como Cmáx, AUC, tiempo hasta la Cmáx (Tmáx), V, t½ de eliminación y CL, con un análisis exploratorio de la posible correlación con diversas características basales (por ejemplo, edad y estado relativo a UGT1A1).
? Medidas específicas de la utilización de recursos sanitarios.
? Cuantificación de CTC y evaluación de varios biomarcadores (por ejemplo, expresión de la topoisomerasa 1 y 2, lesión del ADN y apoptosis en el momento basal); variación con respecto al momento basal.

E.5.2.1

Timepoint(s) of evaluation of this end point

Every 8 weeks (+/- 7 days)

Cada 8 semanas (± 7 días)

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

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

Belgium

Canada

China

France

Germany

Ireland

Israel

Italy

Korea, Republic of

Netherlands

Poland

Russian Federation

Spain

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

The ?end of the trial? is defined as the final data collection date for primary outcome measure.

El ?final del ensayo? se define como la fecha en que se cumplan las condiciones para realizar el análisis estadístico final.

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:

672

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

168

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

141

F.4.2.2

In the whole clinical trial

840

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)

See Protocol

Ver Protocolo

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

2012-07-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-04-08

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