Clinical Trials Register

Summary
EudraCT Number:	2008-000579-12
Sponsor's Protocol Code Number:	D4200L00009
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:	2008-10-14
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

2008-000579-12

A.3

Full title of the trial

A randomised, double-blind, parallel-group, multicentre, phase ii study to evaluate the safety and pharmacological activity of the combination of Vandetanib (100 or 300 mg/daily or placebo) with Fulvestrant (loading dose), in postmenopausal advanced breast cancer patients

Studio randomizzato, doppio placebo, doppio cieco, a gruppi paralleli, multicentrico, di fase II, per valutare la sicurezza e l'attivita' farmacologica della combinazione di vandetanib(100 o 300 mg/die o placebo) con Fulvestrant (dose di carico) in donne in postmenopausa con carcinoma della mammella in stadio avanzato

A.3.2

Name or abbreviated title of the trial where available

ZACFAST

A.4.1

Sponsor's protocol code number

D4200L00009

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ASTRAZENECA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ASTRAZENECA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ASTRAZENECA
B.5.2	Functional name of contact point	ASTRAZENECA
B.5.3	Address:
B.5.3.1	Street Address	PALAZZO VOLTA VIA F. SFORZA
B.5.3.2	Town/ city	BASIGLIO
B.5.3.3	Post code	20080
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390298011
B.5.5	Fax number	+390298011
B.5.6	E-mail	FLORE.LATOUR@ASTRAZENECA.COM

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vandetanib
D.3.2	Product code	ZD6474
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vandetanib
D.3.9.1	CAS number	338992-00-0
D.3.9.2	Current sponsor code	ZD6474
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vandetanib
D.3.2	Product code	ZD6474
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vandetanib
D.3.9.1	CAS number	338992-00-0
D.3.9.2	Current sponsor code	ZD6474
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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: 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	FASLODEX*IM 1SIR 5ML+1AGO
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fulvestrant
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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

Postmenopausal women with advanced breast cancer

Donne in postmenopausa con carcinoma della mammella in stadio avanzato

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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess the event-free survival (EFS) defined as the time from randomisation to progression, death without progression, loss to follow up, whichever occurred first.

L'obiettivo principale dello studio e' di valutare la sicurezza e l'attivita' farmacologica della combinazione di vandetanib(100 o 300 mg/die o placebo) con fulvestrant (LD) nel prolungamento dell' sopravvivenza libera da eventi (Event-Free Survival EFS) in pazienti in postmenopausa con carcinoma della mammella in stadio avanzato.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are are to assess:
• Success rate at six months, defined as the percentage of patients without
progression and still on treatment at 24 weeks (progression, death without
progression, loss to follow up are all failures)
• Objective tumor Response rates (complete response, CR and partial response, PR)
according to RECIST criteria
• Time To Progression
• Progression Free Survival
• Overall survival
• Safety and tolerability of vandetanib / Placebo in combination with fulvestrant
• Quality of Life (EORTC QLQ-C30 questionnaire)

·Il tasso di successi a 6 mesi.
·Il tasso di risposte tumorali obiettive (risposta completa [CR] e parziale [PR]) secondo i criteri RECIST.
·Il Tempo alla Progressione
·La sopravvivenza libera da progressione (Progression-Free Survival PFS)
·La sopravvivenza globale
·La tollerabilita' e la sicurezza.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent
2. Post menopausal woman, defined as a woman fulfilling any 1 of the following
criteria
3. Histologically or cytologically confirmed carcinoma of the breast
4. Patients with metastatic or locally advanced disease not amenable to therapy with
curative intent
5. Patients may have either measurable or non-measurable disease, as defined by
RECIST criteria
6. Must have estrogen receptor ER + and/or progesterone receptor PR+ on primary or
secondary tumour
7. Either patients relapsing during adjuvant treatment or patients presenting with
locally advanced or metastatic breast cancer
8. One previous chemotherapy for advanced disease is allowed (patients who have
stable but evident disease after chemotherapy are eligible)
9. One previous hormone therapy for advanced disease is allowed
10. Neoadjuvant or adjuvant therapy for breast cancer is allowed
11. Patients must have an ECOG PS < 2 and a life expectancy of at least 12 weeks.

1.Rilascio del Consenso Informato Scritto
2.Donne in postmenopausa naturale o artificialmente indotta
3.Conferma istologica o citologica, di carcinoma della mammella
4.Pazienti con malattia metastatica o localmente avanzata
5.Patienti con malattia misurabile o non-misurabile, come definito dai criteri RECIST
6.Pazienti con Recettori per gli Estrogeni ER e/o per il Progesterone PgR positivi
7.Sia pazienti in ricaduta durante trattamento adiuvante sia pazienti con presenza di malattia metastatica o localmente advanzata
8.Una precedente chemioterapia per malattia avanzata e' ammessa (pazienti che sono stabili ma con malattia evidente dopo chemioterapia sono eleggibili)
9.Una precedente ormonoterapia per malattia avanzata e' ammessa
10.Sono ammesse precedenti terapie neoadiuvante o adiuvante
11.Performance Status ECOG 0-1-2 e aspettativa di vita di almeno 12 settimane.

E.4

Principal exclusion criteria

1. Hormone receptor negative tumours (ER and PgR negative)
2. Prior therapy with fulvestrant or prior treatment with VEGFR TKIs (previous
treatment with bevacizumab [Avastin] is permitted)
3. More than one previous hormone-therapy for the advanced disease as defined
before
4. More than one previous chemo-therapy for the advanced disease as defined before
5. CNS metastases
6. Presence of life-threatening metastatic visceral disease, defined as extensive
hepaticinvolvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitic spread. Patients with discrete
pulmonary parenchymal metastases are eligible, provided their respiratory function
is not clinically and significantly compromised as a result of disease

1.Pazienti con Recettori per gli Estrogeni ER e per il Progesterone PgR negativi
2.Precedente trattamento con Fulvestrant o con farmaci inibitori della tirosina chinasi del VEGFR (il precedente trattamento adiuvante con bevacizumab [Avastin] e' consentito)
3.Piu' di una precedente ormonoterapia per malattia avanzata
4.Piu' di una precedente chemioterapia per malattia avanzata
5.Metastasi cerebrali
6.Presenza di malattia metastatica viscerale life-threatening

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is to assess the event-free survival (EFS) defined as the time from randomisation to progression, death without progression, loss to follow up, whichever occurred first.

L'obiettivo primario di questo studio e' la sopravvivenza libera da eventi definita come tempo dalla randomizzazione alla progressione , morte in assenza di progressione o perdita di follow up.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

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

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	135

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

2008-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-09-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-09-28

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