Clinical Trials Register

Summary
EudraCT Number:	2012-000114-10
Sponsor's Protocol Code Number:	LF-PB/11/04
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:	2012-10-11
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-000114-10

A.3

Full title of the trial

A Randomized, Double-Blind, Double Dummy, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy of LF-PB 10 mg, 20 mg, and 30 mg to Treat Lymphorrhea Post Axillary Dissection in Breast Cancer

Studio randomizzato in doppio-cieco, controllato verso placebo, a gruppi paralleli, per valutare l`Efficacia di LF-PB 10 mg, 20 mg, and 30 mg per trattare la linforrea dopo resezione ascellare in pazienti affetti da tumore alla mammella.

A.3.1

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

A randomized double-blind study, performed with the use of placebo, to assess the efficacy of the drug LF-PB at different doses to treat linforrea after removal of axillary lymph nodes in patients with breast cancer.

Studio randomizzato in doppio-cieco, con l`utilizzo di placebo, per valutare l’Efficacia del farmaco LF-PB a diversi dosaggi per trattare la linforrea dopo rimozione dei linfonodi ascellari in pazienti affetti da tumore alla mammella.

A.4.1

Sponsor's protocol code number

LF-PB/11/04

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	CHEMI S.P.A.
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	Chemi S.p.A.
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	Chemi S.p.A.
B.5.2	Functional name of contact point	Sara Manzoni - Clinical R&D Dept.
B.5.3	Address:
B.5.3.1	Street Address	Via dei Lavoratori, 54
B.5.3.2	Town/ city	Cinisello Balsamo (MI)
B.5.3.3	Post code	20092
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 02 6443 2521
B.5.5	Fax number	+39 02 6443 3554
B.5.6	E-mail	s.manzoni@italfarmaco.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	NA
D.3.2	Product code	LF-PB
D.3.4	Pharmaceutical form	Powder and solvent for 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	OCTREOTIDE
D.3.9.1	CAS number	79517-01-4
D.3.9.2	Current sponsor code	LF-PB
D.3.9.3	Other descriptive name	Octreotide acetate
D.3.9.4	EV Substance Code	SUB09417MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	up to
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: 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	NA
D.3.2	Product code	LF-PB
D.3.4	Pharmaceutical form	Powder and solvent for 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	OCTREOTIDE
D.3.9.1	CAS number	79517-01-4
D.3.9.2	Current sponsor code	LF-PB
D.3.9.3	Other descriptive name	Octreotide acetate
D.3.9.4	EV Substance Code	SUB09417MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder and solvent for solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patient undergoing breast surgery with axillary lymph node dissection.

Pazienti che hanno subito asportazione del tumore alla mammella con dissezione dei linfonodi ascellari.

E.1.1.1

Medical condition in easily understood language

Patient undergoing breast surgery with axillary lymph node removal.

Pazienti che hanno subito rimozione dei linfonodi ascellari dopo asportazione del tumore alla mammella.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	SOC
E.1.2	Classification code	10005329
E.1.2	Term	Blood and lymphatic system disorders
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

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 effect of the extended release of octreotide (LF-PB) 10 mg, 20 mg, and 30 mg on time to resolution of lymphorrhea
• To evaluate safety and tolerability of LF-PB 10 mg, 20 mg, and 30 mg

• Valutare l’effetto della formulazione a lento rilascio di octreotide (LF-PB) 10 mg, 20 mg, e 30 mg sul tempo di risoluzione della linforrea.
• Valutare la sicurezza e la tollerabilità di LF-PB 10 mg, 20 mg e 30 mg

E.2.2

Secondary objectives of the trial

• To assess the effects of LF-PB 10 mg, 20 mg, and 30 mg on the daily volume of lymph collected from the drain
• To assess the effect of LF-PB 10 mg, 20 mg, and 30 mg on complications related to lymphorrhea
• To evaluate the pharmacokinetic (PK) profile of LF-PB 10 mg, 20 mg, and 30 mg

• Valutare gli effetti di LF-PB 10 mg, 20 mg e 30 mg sul volume giornaliero di linfa raccolta dal drenaggio
• Valutare gli effetti di LF-PB 10 mg, 20 mg e 30 mg sulle complicazioni correlate alla linforrea
• Valutare il profilo farmacocinetico (PK) di LF-PB 10 mg, 20 mg e 30 mg

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Female aged 18 to 80 years inclusive
2.Body mass index ≥18 kg/m2
3.Signed informed consent form
4.Diagnosis of breast cancer (BC)
5.Undergoing breast surgery with axillary lymph node dissection
Note: Collagen powder or fibrin sealant are not permitted.
6.Negative serum pregnancy test for women of childbearing potential
Note: Female patients of childbearing potential should be advised to use adequate contraception if necessary during treatment with octreotide.
7.Aspartate aminotransferase and alanine aminotransferase <1.5 x the upper limit of normal
8.Ability to fully understand all study procedures and to comply with study visits scheduled for the duration of the study

1. Femmine di età comprese tra i 18 e gli 80 anni, estremi inclusi
2. Indice di Massa corporea ≥18 kg/m2
3. Firma del modulo di consenso informato
4. Diagnosi di cancro al seno
5. Sottoposte a chirurgia della mammella con dissezione dei linfonodi ascellari
Nota: polvere collagene o colla di fibrina non sono ammessi.
6. Test di gravidanza sierico negativo per le donne in eta’ fertile.
Nota: le donne potenzialmente fertili devono essere avvisate sull’utilizzo di un adeguato mezzo di contraccezione durante il periodo di trattamento con octeotride.
7. Aspartato aminotransferasi e alanina aminotransferasi <1,5 il limite superiore del valore normale
8. Capacità di comprendere appieno tutte le procedure di studio e di osservare le visite di studio in programma per tutta la durata dello studio.

E.4

Principal exclusion criteria

1. Presence of any of the following conditions: a. Previous axillary surgery b. Previous chemotherapy c. Previous neoadjuvant therapy d. Recurrent BC e. Diabetes f. Cholelithiasis g. Hypothyroidism h. Hepatitis i. Pregnant or lactating j. Human immunodeficiency virus or hepatitis B or C by screening serology 2. History of radiotherapy 3. History of anaphylaxis to study drug 4. Ascertained or presumptive hypersensitivity to the active principle and/or the ingredients of the study drug formulation 5. QTc interval extension at screening or baseline > 450 msec (as the mean of 3 consecutive readings 5 minutes apart) 6. Presence of any disease or use of concomitant medication known to increase the QT interval (see Appendix 2 for a list of such compounds) 7. Clinically significant or relevant abnormal medical history, vital sign, physical examination, electrocardiogram (ECG), or laboratory evaluation finding 8. Current or recurrent disease that could affect the action, absorption, or disposition of the study drug 9. Current or recurrent disease that could affect the results of the clinical or laboratory assessments required for the study 10. Corticosteroids treatment within 1 month prior to surgery

1. Presenza di una delle seguenti condizioni: a. Precedente chirurgia ascellare b. Precedente chemioterapia c. Precedente terapia Neoadiuvante d. Tumore al seno recidivante e. Diabete f. Colelitiasi g. Ipotiroidismo h. Epatite i. Donne in gravidanza o in allattamento j. Presenza del virus dell'immunodeficienza umana o dell'epatite B o C valutata attraverso screening sierologico 2. Storia di radioterapia 3. Storia di reazione allergiche al farmaco in studio 4. Accertata o presunta ipersensibilita’ al principio attivo e/o agli ingredienti della formulazione del farmaco in studio 5. Estensione dell’intervallo del QT alla visita di screening o alla basale > 450 msec (come media di 3 letture consecutive a distanza di 5 minuti di riposo) 6. Presenza di patologia o utilizzo di farmaci concomitanti che influiscono sull’aumento dell’intervallo del QT (vedere Appendice 2 per la lista di tali composti) 7. Rilevante storia clinica o significative anomalie dei segni vitali, dell’esame fisico, dell’ elettrocardiogramma (ECG) o degli esami di laboratorio 8. Correnti o ricorrenti patologie che possono influenzare l’azione, l’ assorbimento e la distribuzione del farmaco in studio 9. Correnti e transitorie patologie che possono avere effetti sui risultati degli esami di laboratorio richiesti dallo studio 10. Trattamento con corticosteroidi entro 1 mese prima dell’intervento

E.5 End points

E.5.1

Primary end point(s)

Duration of lymphorrhea while the drain is in place. End of lymphorrhea will be declared when the lymph volume measured by the patient is <50 mL/day in 2 consecutive daily collections. The reduction to <50ml in two consecutive days must be confirmed by the site. The date of lymphorrhea resolution is defined as the first of the 2 consecutive days when lymph volume collected is <50 mL.

• Durata della linforrea, mentre il drenaggio è in posizione. La fine della linforrea viene dichiarata quando il volume linfatico è <50 ml / die in 2 raccolte giornaliere consecutive. La riduzione a <50 mL in 2 consecutive giorni deve essere confermata dal centro. La data di risoluzione della linforrea e` definita al primo dei 2 consecutivi giorni in cui il volume di linfa raccolto e`<50 mL.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.5.2

Secondary end point(s)

• Daily volume of lymph collected when drain is in place as reported daily by the patient Duration of lymphorrhea when lymph daily volumes >50ml persists after drain removal and lymph is collected by puncture. End of lymphorrhea will be declared when the lymph volume is <50 mL. • Time to drain removal • Percentage of responders at 1 week after surgery. A responder is a patient for whom lymphorrhea is reduced to <50 mL in 2 consecutive daily collections. • Percentage of responders at drain removal. A responder is a patient for whom lymphorrhea is reduced to <50 mL in 2 consecutive daily collections. • Number of complications related to lymphorrhea • PK parameters (Cmax,, Tmax AUC0-t, and possibly AUC0-, t1/2) after 10 mg, 20 mg, and 30 mg LF-PB IM single-dose administration

• Volume di linfa giornaliero raccolto quando il drenaggio e’ nella cavità, come riferito giornalmente dal paziente. • Durata della linforrea dopo la rimozione del drenaggio quando il volume di linfa persiste a >50 mL e la linfa e` raccolta attraverso la puntura. La fine della linforrea sara` dichiarata quando il volume di linfa e` <50 mL. • Tempo di rimozione del drenaggio • Percentuale di risposte ad 1 settimana dopo l’operazione. Un paziente che risponde e’ colui che ha una riduzione della linforrea di <50 mL dopo 2 raccolte giornaliere consecutive. • Numero di complicanze correlate alla linforrea • Parametri di PK (Cmax, Tmax AUC0-t, e possibile AUC0, and t1/2) dopo somministrazione IM a dosaggio singolo di 10 mg, 20 mg e 30 mg LF-PB.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

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

Yes

E.8.1.7.1

Other trial design description

DOUBLE DUMMY

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

120

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)

In accordance with the clinical practice.

In accordo alla pratica clinica

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

2012-10-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-09-30

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