Clinical Trials Register

Summary
EudraCT Number:	2011-003832-30
Sponsor's Protocol Code Number:	11-PIR-11
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-08-07
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

Italy - Italian Medicines Agency

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

Studio BEACON (BrEAst Cancer Outcomes with NKTR-102, Esiti del cancro al seno con NKTR-102): Studio di Fase 3, multicentrico, randomizzato, in aperto su NKTR-102 rispetto al Trattamento di scelta del medico (TPC) nelle pazienti affette da cancro al seno localmente recidivante o metastatico precedentemente trattate con un'antraciclina, un taxano e 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'').

Studio per comparare NKTR-102 (chiamato anche ''farmaco in studio'') con lo standard trattamenti per il cancro al seno (detto anche ''trattamento del medico scelta '').

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	na
B.5.3.2	Town/ city	na
B.5.3.3	Post code	na
B.5.3.4	Country	Italy
B.5.4	Telephone number	+1 862 261 3634
B.5.5	Fax number	na
B.5.6	E-mail	na.na@quintiles.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	NKTR-102
D.3.2	Product code	na
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	1193151-06-2
D.3.9.2	Current sponsor code	NKTR-102
D.3.9.3	Other descriptive name	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	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.3.4	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	33069-62-4
D.3.9.3	Other descriptive name	Paclitaxel albumin
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	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	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.3.4	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	ERIBULIN MESYLATE
D.3.9.1	CAS number	441045-17-6
D.3.9.4	EV Substance Code	SUB31126
D.3.10	Strength
D.3.10.1	Concentration unit	mCi/ml millicurie(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	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.3.4	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	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	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.3.4	Pharmaceutical form	Emulsion 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	VINORELBINE TARTRATE
D.3.9.1	CAS number	125317-39-7
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	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.3.4	Pharmaceutical form	Emulsion 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	ANHYDROUS DOCETAXEL
D.3.9.1	CAS number	114977-28-5
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	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.3.4	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

cancro della mammella localmente ricorrente, il cancro al seno metastatico

E.1.1.1

Medical condition in easily understood language

Metastasic Breast Cancer (MBC)

Cancro alla mammella metastatico

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	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.1.2 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.1.3

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.

Per confrontare la sopravvivenza globale (OS) delle pazienti che ricevono NKTR-102
somministrato una volta ogni 21 giorni a pazienti che ricevono TPC selezionato dalla
seguente elenco di sette terapie endovenose singolo agente: Eribulin,
ixabepilone, vinorelbina, gemcitabina, paclitaxel,
docetaxel o paclitaxel-nab.

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,To evaluate the pharmacoeconomic implications of NKTR-102

Per confrontare il tasso di risposta oggettivo (ORR) per risposta Criteri di valutazione nei tumori solidi (RECIST) versione 1.1
Per confrontare sopravvivenza libera da progressione (PFS)
Per confrontare il tasso di beneficio clinico (CBR) (la proporzione di pazienti
con risposta completa (CR),risposta parziale (PR),o
malattia stabile (SD) per almeno 6 mesi),confrontare durata della risposta (DOR),determinare i profili di sicurezza di NKTR-102 e di trattamento di
Scelta del medico (TPC) (anche di grado 3 e superiori tossicità,
incidenza di riduzioni della dose e l'intensità della dose),confrontare la salute-qualità della vita (QoL) utilizzando il QLQ-C30questionario con il sottoscala BR23,ottenere farmacocinetica (PK) i dati (in pazienti selezionati randomizzati
a NKTR-102Per valutare lePer valutare le implicazioni farmacoeconomici della terapia NKTR-102

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 function

Il paziente è una femmina adulta con citologicamente o istologicamente confermata
carcinoma della mammella per cui singolo agente chemioterapia citotossica
è indicata
• Il paziente può presentare una malattia misurabile o non misurabile dal
RECIST.
• Il paziente ha ricevuto una precedente terapia (somministrato in neoadiuvante,
adiuvante e / o della malattia metastatica) con un antraciclina, un tassano e
capecitabina
• Il paziente ha minimo di 2 e un massimo di 5 citotossica
regimi chemioterapici con l'ultima dose somministrata entro 6
mesi. Un minimo di due regimi chemioterapici dovuto essere per il locale
recidivante e / o malattia metastatica. Tutti hanno ricevuto la terapia prima di una
diagnosi di malattia metastatica (ad esempio, neoadiuvante, adiuvante o ripetute
La terapia adiuvante dopo una resezione secondo) viene conteggiato come uno
regime.
• Il paziente ha Eastern Cooperative Oncology Group (ECOG) le prestazioni
stato di 0 o 1.
• Adeguata ematopoietico, funzionalità epatica e renale

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

Paziente con la chemioterapia entro 21 giorni, radioterapia entro 14
giorni, la terapia biologica con 14 giorni, la terapia ormonale entro 7 giorni
e la terapia sperimentale entro 21 giorni prima della randomizzazione.
• Paziente con qualsiasi intervento chirurgico importante entro 28 giorni prima della randomizzazione.
• paziente con l'uso concomitante di agenti biologici per il trattamento dei
cancro, compresi gli anticorpi o di qualsiasi farmaco sperimentale (s).
• Paziente con un precedente trattamento per il cancro con un derivato camptotecina.
• pazienti affetti da disturbi gastrointestinali croniche o acute con conseguente diarrea di qualsiasi
grado di gravità; pazienti che stanno assumendo anti-diarrea cronica di supporto
cura per controllare la diarrea nei 28 giorni prima della randomizzazione.
• farmacoterapia paziente ha ricevuto per l'epatite B o C, la tubercolosi o
HIV.
• paziente con cirrosi noto con diagnosi di Child-Pugh classe A o
malattie epatiche superiore.
• Paziente con tumore maligno prima (diverso da cancro al seno) ad eccezione di
non-melanoma, cancro della pelle e carcinoma in situ (o della cervice
vescica), a meno diagnosticati e trattati in via definitiva più di 5 anni
prima della randomizzazione.
• paziente che richiede l'uso quotidiano della supplementazione di ossigeno nei 28 giorni
prima della randomizzazione.
• I pazienti con una insufficienza cardiovascolare

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is OS

over all survival

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 sopravvivenza globale è definito come il tempo dalla data di randomizzazione alla
morte per qualsiasi causa. I pazienti saranno seguiti fino alla loro data di morte o fino alla chiusura finale del database. I pazienti che sono perso-to-follow-up o
vivi al momento dell'analisi sarà censurato nel momento in cui sono stati l'ultima
noto vivo.

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 ; change from baseline.

ORR, PFS,CBR, DOR, incidenza e la severità del trattamento di eventi avversi (TEAEs),
anomalie di laboratorio, i sintomi mirate (tra cui diarrea e
neuropatia); incidenza di riduzioni della dose, intensità di dose
• scala QLQ-C30 individuali, il punteggio complessivo e il valore BR23 punteggio e
cambiano nel tempo della partecipazione allo studio
• I parametri farmacocinetici derivati, comprese le Cmax, AUC, il tempo di Cmax (Tmax), V,
t ½ di eliminazione e di CL, con un'analisi esplorativa in relazione ad eventuali
correlazione con le caratteristiche di base diverse (ad esempio, età e UGT1A1
status)
• misure selezionati di utilizzo sanitario
• Quantificazione delle CTC e la valutazione di biomarcatori diversi , cambiamenti dalla visita basale

E.5.2.1

Timepoint(s) of evaluation of this end point

Every 8 weeks (+/- 7 days)

ogni 8 sett, finestra di 7 giorni

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

Number of subjects for this age range:

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

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

840

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)

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

2012-07-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-19

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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