Clinical Trials Register

Summary
EudraCT Number:	2011-002002-70
Sponsor's Protocol Code Number:	BIT-2
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-01-23
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

2011-002002-70

A.3

Full title of the trial

A RANDOMISED PHASE II TRIAL OF SECOND LINE THERAPY IN ADVANCED BILIARY TRACT CANCER: CAPECITABINE OR CAPECITABINE PLUS MITOMYCIN C (BIT-2)

STUDIO RANDOMIZZATO DI FASE II DI CHEMIOTERAPIA DI SECONDA LINEA CON CAPECITABINA O CAPECITABINA PIU' MITOMICINA C NEL TRATTAMENTO DELL'ADENOCARCINOMA DELLE VIE BILIARI AVANZATO (BIT-2)

A.3.1

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

TRIAL TO EVALUATE CHEMOTHERAPY WITH CAPECITABINE OR CAPECITABINE PLUS MITOMYCIN C IN ADVANCED BILIARY TRACT CANCER

STUDIO PER LA VALUTAZIONE DEL TRATTAMENTO DI CHEMIOTERAPIA CON CAPECITABINA O CAPECITABINA PIU' MITOMICINA C NELLA NEOPLASIA DELLE VIE BILIARI

A.4.1

Sponsor's protocol code number

BIT-2

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	FONDAZIONE CENTRO S. RAFFAELE DEL MONTE TABOR
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Regione Lombardia
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	Fondazione Centro San Raffaele del Monte Tabor
B.5.2	Functional name of contact point	Oncologia Medica
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina, 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	02 26437644
B.5.5	Fax number	02 26437603
B.5.6	E-mail	cereda.stefano@hsr.it

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	Yes
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	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	CAPECITABINE
D.3.9.1	CAS number	154361-50-9
D.3.9.4	EV Substance Code	SUB12474MIG
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	150
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	Yes
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	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	CAPECITABINE
D.3.9.1	CAS number	154361-50-9
D.3.9.4	EV Substance Code	SUB12474MIG
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	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
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	Powder for 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.3.8	INN - Proposed INN	MITOMYCIN C
D.3.9.1	CAS number	50-07-7
D.3.9.4	EV Substance Code	SUB20671
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	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: 4
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	Yes
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	Powder for 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.3.8	INN - Proposed INN	MITOMYCIN C
D.3.9.1	CAS number	50-07-7
D.3.9.4	EV Substance Code	SUB20671
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.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 advanced or metastatic adenocarcinoma of the biliary tract (intra or extra-hepatic biliary ducts, gallbladder, Ampulla of Vater).

Adenocarcinoma delle vie biliari (vie biliari intra ed extraepatiche, colecisti, ampulla di Vater) localmente avanzato o metastatico.

E.1.1.1

Medical condition in easily understood language

Cancer of the biliary tract.

Tumore delle vie biliari.

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	LLT
E.1.2	Classification code	10025734
E.1.2	Term	Malignant neoplasm of biliary tract, part unspecified
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

Assessment of the therapeutic activity of capecitabine alone or in combination with mitomycin C in terms of progression-free survival rate at 6 months from treatment start in patients with advanced/metastatic biliary adenocarcinoma in progression after gemcitabine and platinum compounds.

Valutare l'attivita' terapeutica di capecitabina, somministrata da sola o in combinazione con mitomicina C, in termini di progressione libera da malattia (PFS) a 6 mesi, in pazienti affetti da adenocarcinoma delle vie biliari localmente avanzato o metastatico, in progressione di malattia dopo I linea standard di trattamento con gemcitabina e analoghi del platino.

E.2.2

Secondary objectives of the trial

1. Assessment of additional measures of tumor control to further characterize the efficacy profile of capecitabine alone or in combination with mitomycin C. 2. Evaluation of the safety profile of capecitabine alone or in combination with mitomycin C. 3. Study of the prognostic / predictive role of proteic markers.

1. Valutazione di ulteriori parametri di misurazione del controllo tumorale per caratterizzare ulteriormente il profilo di efficacia di capecitabina somministrata da sola o in combinazione con mitomicina C. 2. Valutazione del profilo di tollerabilita' di capecitabina somministrata da sola o in combinazione con mitomicina C. 3. Studio del ruolo prognostico / predittivo di marcatori proteici.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed and dated IRB/IEC-approved Informed Consent. 2. Diagnosis of locally advanced or metastatic adenocarcinoma of the biliary tract (Ampulla of Vater, gallbladder, intra or extra-hepatic biliary ducts). 3. Disease progressing after first-line chemotherapy with gemcitabine and platinum analogs (only one prior systemic therapy allowed). 4. Age 18-75 years and Karnofsky Performance Status > 50%. 5. Adequate bone marrow, liver and kidney function.

1. Modulo di consenso informato, approvato dal Comitato Etico, firmato e datato. 2. Diagnosi di adenocarcinoma localmente avanzato o metastatico delle vie biliari (ampulla di Vater, cistifellea, dotti biliari intra o extra-epatici). 3. Malattia in progressione dopo una prima linea di chemioterapia con gemcitabina piu' un analogo del platino (una sola linea di terapia sistemica precedente permessa). 4. Eta' 18-75 anni e condizioni generali valutate con la scala Karnofsky > 50%. 5. Funzionalita' adeguate per midollo osseo, fegato e reni.

E.4

Principal exclusion criteria

1. Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasm without evidence of disease at least from 5 years. 2. Known brain metastases. 3. Clinically significant cardiovascular disease </= 1 year prior to dosing. 4. Clinically significant disease including Cerebral Vascular Accident. 5. History of interstitial lung disease or evidence of interstitial lung disease on baseline chest CT scan. 6. Known positive tests for human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C. 7. Subject who is pregnant or breast feeding. 8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

1. Precedenti o concomitanti neoplasie ad altri siti negli ultimi 5 anni, con l'eccezione del carcinoma in situ della cervice curato chirurgicamente e del carcinoma basale a cellule squamose della pelle e altri neoplasmi senza evidenza di malattia. 2. Metastasi cerebrali note. 3. Malattie cardiovascolari clinicamente significative entro un anno dall'inizio del trattamento. 4. Malattie clinicamente significative quali l'insufficienza cerebro-vascolare. 5. Storia di malattia polmonare interstiziale o evidenza di malattia polmonare interstiziale all'esame radiologico basale. 6. Positivita' nota al test del virus dell'immunodeficienza (HIV), infezioni attive del virus dell'epatite B e C. 7. Soggetti in gravidanza o in allattamento. 8. Presenza di qualsiasi condizione psicologica, famigliare, sociologica o geografica che possano potenzialmente ostacolare una corretta partecipazione allo studio.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival rate at 6 months from treatment start (PFS-6 rate).

Sopravvivenza libera da progressione a 6 mesi dall'inizio del trattamento (tasso PFS-6).

E.5.1.1

Timepoint(s) of evaluation of this end point

At 6 months from treatment start.

A 6 mesi dall'inizio del trattamento.

E.5.2

Secondary end point(s)

1. Progression-free survival. 2. Overall Survival (OS). 3. Objective Response Rate (CR+PR), Disease Control Rate, Duration of Response. 4. Overall safety profile. 5. Basal expression of thymidine synthase and thymidine phosphorylase in tumor.

1. Sopravvivenza libera da progressione. 2. Sopravvivenza (OS). 3. Tasso di risposta obiettiva confermata (CR + PR), Tasso di controllo della malattia, Durata della risposta. 4. Profilo di tollerabilita' generale. 5. Espressione basale di timidina sintetasi e timidina fosforilasi nel tumore.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Time of disease progression. 2. Date of death. 3. All treatment period. 4. All cycles, from enrollment to 42 days after last treatment. 5. At the end of the study.

1. Il momento della progressione della malattia. 2. La data del decesso. 3. Tutta la durata del trattamento. 4. Tutti i cicli, dall'arruolamento fino a 42 giorni dopo l'ultimo trattamento. 5. Al termine della sperimentazione.

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

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

Yes

E.6.13.1

Other scope of the trial description

Study of the prognostic / predictive role of proteic markers.

Studio del ruolo prognostico / predittivo di marcatori proteici.

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

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

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 including follow up.

LVLS incluso il follow up.

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

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.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)

Standard medical care for that condition.

Terapie per la patologia secondo la 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

2011-07-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-05-06

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